Author: "Profico, D" - Searchworks@Jio Institute Digital Library Search Results

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1. Human neural stem cells derived from fetal human brain communicate with each other and rescue ischemic neuronal cells through tunneling nanotubes

Author: Capobianco, D. L., De Zio, R., Profico, D. C., Gelati, M., Simone, L., D’Erchia, A. M., Di Palma, F., Mormone, E., Bernardi, P., Sbarbati, A., Gerbino, A., Pesole, G., Vescovi, A. L., Svelto, M., and Pisani, F.
Published: 2024
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2. Preliminary data of intracerebroventricular transplantation of human-Neural Stem Cells in a mouse model of Amyotrophic Lateral Sclerosis

Author: Vulcano, E, Lombardi, I, Rasà, D, Ferrero, C, Perciballi, E, Ferro, S, Carletti Rose, M, Gelati, M, Profico, D, Mazzini, L, Vercelli, A, Vescovi, A, Boido, M, Ferrari, D, Vulcano Edvige, Lombardi Ivan, Rasà Daniela, Ferrero Clelia, Perciballi Elisa, Ferro Sara, Carletti Rose Mary, Gelati Maurizio, Profico Daniela, Mazzini Letizia, Vercelli Alessandro, Vescovi Angelo Luigi, Boido Marina, Ferrari Daniela, Vulcano, E, Lombardi, I, Rasà, D, Ferrero, C, Perciballi, E, Ferro, S, Carletti Rose, M, Gelati, M, Profico, D, Mazzini, L, Vercelli, A, Vescovi, A, Boido, M, Ferrari, D, Vulcano Edvige, Lombardi Ivan, Rasà Daniela, Ferrero Clelia, Perciballi Elisa, Ferro Sara, Carletti Rose Mary, Gelati Maurizio, Profico Daniela, Mazzini Letizia, Vercelli Alessandro, Vescovi Angelo Luigi, Boido Marina, and Ferrari Daniela
Published: 2024

3. Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis

Author: Leone, M, Gelati, M, Profico, D, Gobbi, C, Pravata, E, Copetti, M, Conti, C, Abate, L, Amoruso, L, Apollo, F, Balzano, R, Bicchi, I, Carella, M, Ciampini, A, Colosimo, C, Crociani, P, D'Aloisio, G, Di Viesti, P, Ferrari, D, Fogli, D, Fontana, A, Frondizi, D, Grespi, V, Kuhle, J, Laborante, A, Lombardi, I, Muzi, G, Paci, F, Placentino, G, Popolizio, T, Ricciolini, C, Sabatini, S, Silveri, G, Spera, C, Stephenson, D, Stipa, G, Tinella, E, Zarrelli, M, Zecca, C, Ventura, Y, D'Alessandro, A, Peruzzotti-Jametti, L, Pluchino, S, Vescovi, A, Leone M. A., Gelati M., Profico D. C., Gobbi C., Pravata E., Copetti M., Conti C., Abate L., Amoruso L., Apollo F., Balzano R. F., Bicchi I., Carella M., Ciampini A., Colosimo C., Crociani P., D'Aloisio G., Di Viesti P., Ferrari D., Fogli D., Fontana A., Frondizi D., Grespi V., Kuhle J., Laborante A., Lombardi I., Muzi G., Paci F., Placentino G., Popolizio T., Ricciolini C., Sabatini S., Silveri G., Spera C., Stephenson D., Stipa G., Tinella E., Zarrelli M., Zecca C., Ventura Y., D'Alessandro A., Peruzzotti-Jametti L., Pluchino S., Vescovi A. L., Leone, M, Gelati, M, Profico, D, Gobbi, C, Pravata, E, Copetti, M, Conti, C, Abate, L, Amoruso, L, Apollo, F, Balzano, R, Bicchi, I, Carella, M, Ciampini, A, Colosimo, C, Crociani, P, D'Aloisio, G, Di Viesti, P, Ferrari, D, Fogli, D, Fontana, A, Frondizi, D, Grespi, V, Kuhle, J, Laborante, A, Lombardi, I, Muzi, G, Paci, F, Placentino, G, Popolizio, T, Ricciolini, C, Sabatini, S, Silveri, G, Spera, C, Stephenson, D, Stipa, G, Tinella, E, Zarrelli, M, Zecca, C, Ventura, Y, D'Alessandro, A, Peruzzotti-Jametti, L, Pluchino, S, Vescovi, A, Leone M. A., Gelati M., Profico D. C., Gobbi C., Pravata E., Copetti M., Conti C., Abate L., Amoruso L., Apollo F., Balzano R. F., Bicchi I., Carella M., Ciampini A., Colosimo C., Crociani P., D'Aloisio G., Di Viesti P., Ferrari D., Fogli D., Fontana A., Frondizi D., Grespi V., Kuhle J., Laborante A., Lombardi I., Muzi G., Paci F., Placentino G., Popolizio T., Ricciolini C., Sabatini S., Silveri G., Spera C., Stephenson D., Stipa G., Tinella E., Zarrelli M., Zecca C., Ventura Y., D'Alessandro A., Peruzzotti-Jametti L., Pluchino S., and Vescovi A. L.
Abstract: We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.
Published: 2023

4. Culturing and Expansion of “Clinical Grade” Neural Stem Cells from the Fetal Human Central Nervous System

Author: Deleyrolle, LP, Gelati, M, Profico, D, Ferrari, D, Vescovi, A, Gelati M., Profico D. C., Ferrari D., Vescovi A. L., Deleyrolle, LP, Gelati, M, Profico, D, Ferrari, D, Vescovi, A, Gelati M., Profico D. C., Ferrari D., and Vescovi A. L.
Abstract: NSCs have been demonstrated to be very useful in grafts into the mammalian central nervous system to investigate the exploitation of NSC for the therapy of neurodegenerative disorders in animal models of neurodegenerative diseases. To push cell therapy in CNS on stage of clinical application, it is necessary to establish a continuous and standardized, clinical grade (i.e., produced following the good manufacturing practice guidelines) human neural stem cell lines. In this chapter we will illustrate some of the protocols for the production and characterization routinely used into our GMP “cell factory” for the production of “clinical grade” human neural stem cell lines already in use in clinical trials on neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS— Clinicaltrials.gov number NCT01640067) and secondary progressive multiple sclerosis (SPMS— Clinicaltrials.gov number NCT03282760).
Published: 2022

5. Human Neural Stem Cell-Based Drug Product: Clinical and Nonclinical Characterization

Author: Profico, D, Gelati, M, Ferrari, D, Sgaravizzi, G, Ricciolini, C, Projetti Pensi, M, Muzi, G, Cajola, L, Copetti, M, Ciusani, E, Pugliese, R, Gelain, F, Vescovi, A, Profico D. C., Gelati M., Ferrari D., Sgaravizzi G., Ricciolini C., Projetti Pensi M., Muzi G., Cajola L., Copetti M., Ciusani E., Pugliese R., Gelain F., Vescovi A. L., Profico, D, Gelati, M, Ferrari, D, Sgaravizzi, G, Ricciolini, C, Projetti Pensi, M, Muzi, G, Cajola, L, Copetti, M, Ciusani, E, Pugliese, R, Gelain, F, Vescovi, A, Profico D. C., Gelati M., Ferrari D., Sgaravizzi G., Ricciolini C., Projetti Pensi M., Muzi G., Cajola L., Copetti M., Ciusani E., Pugliese R., Gelain F., and Vescovi A. L.
Abstract: Translation of cell therapies into clinical practice requires the adoption of robust production protocols in order to optimize and standardize the manufacture and cryopreservation of cells, in compliance with good manufacturing practice regulations. Between 2012 and 2020, we conducted two phase I clinical trials (EudraCT 2009-014484-39, EudraCT 2015-004855-37) on amyotrophic lateral sclerosis secondary progressive multiple sclerosis patients, respectively, treating them with human neural stem cells. Our production process of a hNSC-based medicinal product is the first to use brain tissue samples extracted from fetuses that died in spontaneous abortion or miscarriage. It consists of selection, isolation and expansion of hNSCs and ends with the final pharmaceutical formulation tailored to a specific patient, in compliance with the approved clinical protocol. The cells used in these clinical trials were analyzed in order to confirm their microbiological safety; each batch was also tested to assess identity, potency and safety through morphological and functional assays. Preclinical, clinical and in vitro nonclinical data have proved that our cells are safe and stable, and that the production process can provide a high level of reproducibility of the cultures. Here, we describe the quality control strategy for the characterization of the hNSCs used in the above-mentioned clinical trials.
Published: 2022

6. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

Author: Marzona, Irene, Avanzini, Fausto, Lucisano, Giuseppe, Tettamanti, Mauro, Baviera, Marta, Nicolucci, Antonio, Roncaglioni, Maria Carla, Tombesi, M., Tognoni, G., Massa, E., Marrocco, W., Micalella, M., Caimi, V., Longoni, P., Avanzini, F., Franzosi, M. G., Roncaglioni, M. C., Marzona, I., Baviera, M., Monesi, L., Pangrazzi, I., Barlera, S., Milani, V., Nicolis, E., Casola, C., Clerici, F., Palumbo, A., Sgaroni, G., Marchioli, R., Silletta, M. G., Pioggiarella, R., Scarano, M., Marfisi, R. M., Flamminio, A., Macino, L., Ferri, B., Pera, C., Polidoro, A., Abbatino, D., Acquati, M., Addorisio, G., Adinolfi, D., Adreani, L., Agistri, M. R., Agneta, A., Agnolio, M. L., Agostini, N., Agostino, G., Airò, A., Alaimo, N., Albano, M., Albano, N., Alecci, G., Alemanno, S., Alexanian, A., Alfarano, M., Alfè, L., Alonzo, N., Alvino, S., Ancora, A., Andiloro, S., Andreatta, E., Angeli, S., Angiari, F., Angilletti, V., Annicchiarico, C., Anzivino, M., Aprea, R., Aprile, A., Aprile, E., Aprile, I., Aprile, L., Armellani, V., Arnetoli, M., Aronica, A., Autiero, V., Bacca, G., Baccalaro, A. M., Bacci, M., Baglio, G., Bagnani, M., Baiano, A., Baldari, A., Ballarini, L., Banchi, G., Bandera, R., Bandini, F., Baratella, M., Barbieri, A., Barbieri Vita, A., Bardi, M., Barlocchi, M., Baron, P., Bartoli, M., Basile, A., Basile, F., Basile, S., Battaggia, A., Battaglia, A., Baù, A., Beconcini, G., Beggio, R., Belfiore, P. A., Belicchi, M., Bellamoli, S., Bellini, C., Bellomo, M., Benetollo, C., Benetti, R., Beretta, E., Bertalero, P., Bertaso, F. G., Bertolani, U., Bettelli, G., Biagiotti, G., Bianchi, S., Bianco, G., Biccari, F., Bigioli, F., Bindi, M., Bisanti, G., Bitetti, E. M., Blasetti, M. P., Blesi, F., Boato, V., Boga, S., Boidi, E., Boldrin, G., Bollati, A., Bolzan, L., Bolzonella, S., Bonardi, P., Bonato, G. B., Bonci, M., Bonfitto, G., Bonincontro, E., Boninsegna, F., Bonissone, D., Bono, L., Bonollo, E., Borghi, M., Borioli, N., Borsatto, M., Bosco, T., Bosisio Pioltelli, M., Botarelli, C., Botassis, S., Bottini, F., Bottos, C., Bova, G., Bova, V., Bozzani, A., Bozzetto, R. M., Braga, V. T., Braglia, M., Bramati, E., Brazzoli, C., Breglia, G., Brescia, A., Briganti, D., Brigato, G., Brocchi, A., Brosio, F. A., Bruni, E., Buscaglia, E., Bussini, M. D., Bussotti, A., Buzzaccarini, F., Buzzatti, A., Caccamo, G., Cacciavillani, C., Caggiano, G., Caimi, V., Calciano, F. P., Calderisi, M., Calienno, S., Caltagirone, P., Calzolari, I., Cammisa, M., Campanaro, M., Campanella, G. B., Campese, F., Canali, G., Candiani, D. E. L., Canepa, R., Canini, D., Canino, A., Cantoro, E. A., Capilupi, V., Capotosto, P., Cappelli, B., Capraro, G., Carafa, F. A., Carano, Q., Carcaterra, V., Carriero, D., Carrozzo, G., Cartanese, M., Casalena, M., Casarola, M., Caso, C., Casotto, M., Castaldi, F., Castegnaro, R., Castellani, G., Castri, S., Catalano, E., Catinello, N., Caturano, G., Cavallaro, R., Cavallo, A. M., Cavallo, G., Cavion, M. T., Cavirani, G., Cazzaniga, F., Cazzetta, D., Cecconi, V., Cefalo, A., Celebrano, M., Celora, A., Centonze, P., Cerati, D., Cesaretti, D., Checchia, G., Checchin, A., Cherubini, M., Chianese, L., Chiappa, A., Chiappa, M. V., Chiariello, G., Chiavini, G., Chicco, M., Chiumeo, F., Ciacciarelli, A., Ciaci, D., Ciancaglini, R., Cicale, C., Cicale, S., Cipolla, A., Ciruolo, A., Citeri, A. L., Citterio, G., Clerici, M., Coazzoli, E., Collecchia, G., Colletta, F., Colombo, I., Colorio, P., Coluccia, S., Comerio, M., Comoretto, P., Compagni, M., Conte, O., Contri, S., Contrisciani, A., Coppetti, T., Corasaniti, F., Corradi, M. T., Corsano, A., Corsini, A., Corti, N., Costantini, G., Costantino, A., Cotroneo, S., Cozzi, D., Cravello, M. G., Cristiano, E., Cucchi, R., Cusmai, L., D’Errico, G. B., D’Agostino, P., Dal Bianco, L., Dal Mutto, U., Dal Pozzo, G., Dallapiccola, P., Dallatorre, G., Dalle Molle, G., Dalloni, E., D’Aloiso, A., D’Amicis, G., Danese, R., Danieli, D., Danisi, G., D’Anna, M. A., Danti, G., D’Ascanio, S., Davidde, G., De Angeli, D., De Bastiani, R., De Battisti, A., De Bellis, A., De Berardinis, G., De Carlo, F., De Giorgi, D., De Gobbi, R., De Lorenzis, E., De Luca, P., De Martini, G., De Marzi, M., De Matteis, D., De Padova, S., De Polo, P., De Sabato, N., De Stefano, T., De Vita, M. T., De Vito, U., De Zolt, V., Debernardi, F., Del Carlo, A., Del Re, G., Del Zotti, F., D’Elia, R., Della Giovanna, P., Dell’Acqua, L., Dell’Orco, R. L., Demaria, G., Di Benedetto, M. G., Di Chiara, G., Di Corcia, V., Di Domizio, O., Di Donato, P., Di Donato, S., Di Fermo, G., Di Franco, M., Di Giovannantonio, G., Di Lascio, G., Di Lecce, G., Di Lorenzo, N., Di Maro, T., Di Mattia, Q., Di Michele, E., Di Modica, R. S., Di Murro, D., Di Noi, M. C., Di Paoli, V., Di Santi, M., Di Sanzo, A., Di Turi, C., Diazzi, A., Dileo, I., D’Ingianna, A. P., Dolci, A., Donà, G., Donato, C., Donato, P., Donini, A., Donna, M. E., Donvito, T. V., Esposito, L., Esposito, N., Evangelista, M., Faita, G., Falco, M., Falcone, D. A., Falorni, F., Fanciullacci, A., Fanton, L., Fasolo, L., Fassina, R., Fassone, A., Fatarella, P., Fedele, F., Fera, I., Fera, L., Ferioli, S., Ferlini, M. G., Ferlino, R., Ferrante, G., Ferrara, F. N., Ferrarese, M. F., Ferrari, G., Ferrari, O., Ferreri, A., Ferroni, M., Fezzi, G., Figaroli, C., Fina, M. G., Fioretta, A., Fiorucci, C., Firrincieli, R., Fischetti, M., Fischietti, G., Fiume, D. C., Flecchia, G., Forastiere, G., Fossati, B., Franceschi, P. L., Franchi, L., Franzoso, F., Frapporti, G., Frasca, G., Frisotti, A., Fumagalli, G., Fusco, D., Gabriele, P., Gabrieli, A., Gagliano, D., Galimberti, G., Galli, A., Gallicchio, N., Gallio, F., Gallipoli, T., Gallo, P., Galopin, T., Gambarelli, L., Garbin, A., Garozzo, G. M., Gasparri, R., Gastaldo, M., Gatti, E., Gazzaniga, P., Gennachi, N., Gentile, R. V., Germani, P., Gesualdi, F., Gherardi, E., Ghezzi, C., Ghidini, M. G., Ghionda, F., Giacci, L., Gialdini, D., Giampaolo, C., Giancane, R., Giannanti, A., Giannese, S., Giannini, L., Giaretta, M., Giaretta, R., Giavardi, L., Giordano, P., Giordano, E., Giordano, B., Gioria, G. M., Giugliano, R., Grassi, E. A., Greco, A., Greco, L., Grilletti, N., Grimaldi, N., Grisetti, G., Groppelli, G., Gualtieri, L., Guarducci, M., Guastella, G., Guerra, M., Guerrini, F., Guglielmini, A., Guido, A., Gulotta, P., Iacono, E., Iadarola, G., Ianiro, G., Iarussi, V., Ieluzzi, M. L., Ierardi, C., Ingaldi, F., Interlandi, S., Iocca, M., Iorno, A., Ioverno, E., Iurato, R., La Pace, L., La Piscopia, C., La Selva, R., Lafratta, M., Lamparelli, M., Lanaro, G., Lancerotto, R., Larcher, M., Lassandro, M., Lattuada, G., Laurino, P., Lefons, C., Legrottaglie, F., Lemma, A., Leone, D., Leone, F., Leso, A., Leuzzi, G., Levato, G., Libardi, L., Libralesso, N., Licini, P. I., Licursi, G., Lidonnici, F., Lillo, C., Liveri, L., Livio, A., Loiero, R. A., Loison, M., Lombardo, G., Lombardo, T., Lomunno, V., Lomuscio, S., Lonedo, A., Longo, E., Longoni, P., Lora, L., Lotterio, A., Lucatello, L., Luongo, A., Lupoli, M., Macchia, C., Macri, G., Mafessanti, M., Maggialetti, V., Maggioni, A., Magnani, M., Maiellaro, G., Mancuso, A., Maniglio, A. R., Mannari, G. L., Manni, A., Manocchio, B., Mao, M., Maranò, A., Maraone, E., Marascio, D., Marcheselli, P., Marchetto, B., Marchetto, S., Marchi, A., Marchi, G. L., Mariano, C., Marinacci, S., Marinelli, S., Marini, G., Marra, V. C., Marrali, F., Marseglia, C., Martello, G., Martino, C., Martino, G., Martino, M., Marulli, C. F., Maruzzi, G., Marzotti, A., Mascheroni, G., Mascolo, P., Masoch, G., Masone, R., Massa, E., Massa, L., Massafra, M., Massi, M., Massignani, D. M., Matarese, A. M., Matini, G., Mauro, R., Mazzi, M., Mazzillo, A., Mazzocato, E., Mazzoleni, N. S., Mazzone, A., Melacci, A., Mele, E., Meliota, P., Menaspà, S., Meneghello, F., Merola, G., Merone, L., Metrucci, A., Mezzina, V., Micchi, A., Michielon, A., Migliore, N., Minero, G., Minotta, F., Mirandola, C., Mistrorigo, S., Modafferi, L., Moitre, R., Mola, E., Monachese, C., Mongiardini, C., Montagna, F., Montani, M., Montemurno, I., Montolli, R., Montorsi, S., Montresor, M., Monzani, M. G., Morabito, F., Mori, G., Moro, A., Mosca, M. F., Motti, F., Muddolon, L., Mugnai, M., Muscas, F., Naimoli, F., Nanci, G., Nargi, E., Nasorri, R., Nastrini, G., Negossi, M., Negrini, A., Negroni, A., Neola, V., Niccolini, F., Niro, C. M., Nosengo, C., Novella, G., Nuti, C., Obici, F., Olita, C., Oliverio, S. S., Olivieri, I., Oriente, S., Orlando, G., Paci, C., Pagano, G., Pagliara, C., Paita, G., Paladini, G., Paladino, G., Palano, T., Palatella, A., Palermo, P., Palmisano, M., Pando, P., Panessa, P., Panigo, F., Panozzo, G., Panvini, F., Panzieri, F., Panzino, A., Panzitta, F., Paoli, N., Papagna, R., Papaleo, M. G., Papalia, G., Parisi, R., Parotti, N., Parravicini, D., Passarella, P., Pastore, G. A., Patafio, M., Pavone, P., Pedroli, W., Pedroni, M., Pelligra, G., Pellizzari, M., Penati, A., Perlot, M., Perrone, A., Perrone, G., Peruzzi, P., Peselli, C., Petracchini, L., Petrera, L., Petrone, S., Peverelli, C., Pianorsi, F., Piazza, G. P., Piazzolla, G., Picci, A., Pienabarca, G., Pietronigro, T. P., Pignocchino, P., Pilone, R., Pinto, D., Pirovano, E., Pirrotta, D., Pisante, V., Pitotto, P., Pittari, L., Piva, A., Pizzoglio, A., Plantera, O. R., Plebani, W., Plessi, S., Podrecca, D., Poerio, V., Poggiani, F., Pogliani, W., Poli, L., Poloni, F. G., Porcelli, R., Porto, S., Pranzo, L., Prevedello, C., Profeta, C., Profico, D., Punzi, A., Quaglia, G. M., Racano, M., Raccone, A., Radice, F., Raho, C. A., Raimondi, R., Rainò, M., Ramponi, R., Ramunni, A., Ramunni, A. L., Ravasio, F., Ravera, M., Re Sartò, G., Rebustello, G., Regazzoli, S., Restelli, C., Rezzonico, M., Ricchiuto, F., Rigo, S., Rigon, G., Rigon, R., Rinaldi, O. V., Rinaldi, M., Risplendente, P. G., Rispoli, M., Riundi, R., Riva, M. G., Rizzi, A. L., Rizzi, D., Rizzo, L. D., Rocchi, L., Rondinone, B., Rosa, B., Rosati, F., Roselli, F., Rossetti, A., Rossetti, C., Rossi, R., Rossi, P. R., Rossi, A., Rossi, C. L., Rossitto, A., Ruffini, R., Ruffo, A., Ruggio, S., Ruo, M., Russo, B., Russo, L., Russo, R., Russo, S., Russo, U., Russo, V., Ruta, G., Sacchi, F., Sacco Botto, F., Saia, A., Salladini, G., Salmoiraghi, S., Saluzzo, F., Salvatore, C., Salvatori, E., Salvio, G., Sandri, P., Sandrini, T., Sangermano, V., Santoni, N., Saracino, A. D., Saracino, A., Sarasin, P., Sardo Infirri, C., Sarrì, B., Sartori, G., Sartori, N., Sauro, C., Scaglioni, M., Scalfi, C., Scamardella, A. M., Scandale, G., Scandone, L., Scannavini, G., Scarati, R., Scardi, A., Scarpa, F. M., Scazzi, P., Schifone, A., Schiroso, G., Scigliano, G., Scilla, A., Sciortino, M., Scolaro, G., Scollo, E., Scorretti, G., Sellitti, R., Selmo, A., Selvaggio, G., Sempio, A., Seren, F., Serio, L., Serra, C., Serra, L., Siciliano, D., Sideri, A., Sighele, M., Signore, R., Siliberto, F., Silvestro, M., Simioni, G., Simmini, G., Simonato, L., Sinchetto, F., Sizzano, E., Smajato, G., Smaldone, M., Sola, G., Sordillo, L., Sovran, C. S., Spagnul, P., Spanò, F., Sproviero, S., Squintani, A., Stella, L., Stilo, V., Stocchiero, B., Stornello, M. C., Stracka, G., Strada, S., Stranieri, G., Stucci, N., Stufano, N., Suppa, A., Susca, V. G., Sutti, M., Taddei, M., Tagliabue, E., Tagliente, G., Talato, F., Talerico, P., Talia, R., Taranto, R., Tartaglia, M., Tauro, N., Tedesco, A., Tieri, P., Tirelli, M., Tocci, L., Todesco, P., Tognolo, M., Tomba, A., Tonello, P., Tonon, R., Toscano, L., Tosi, A., Tosi, G., Toso, S., Travaglio, P., Tremul, L., Tresso, C., Triacchini, P., Triggiano, L., Trigilio, A., Trimeloni, J., Tripicchio, G., Tritto, G. S., Trono, F., Trotta, E., Trotta, G., Tubertini, A., Turri, C., Turri, L., Tuttolani, M. P., Urago, M., Ursini, G., Valcanover, F., Valente, L., Valenti, M., Valentini, F., Vallone, G., Valz, P., Valzano, L., Vanin, V., Vatteroni, M., Vegetti, L., Vendrame, D., Veramonti, I., Veronelli, G., Vesco, A., Vicariotto, G., Vignale, G., Villa, P. L., Vinciguerra, R., Visco, A., Visentin, G., Visonà, E., Vitali, E., Vitali, S., Vitti, F., Volpone, D. A., Zambon, N., Zammarrelli, A., Zanaboni, A., Zane, D., Zanetti, B., Zanibellato, R., Zappetti, M., Zappone, P., Zerilli, G., Zirino, V., Zoccali, R., Zuin, F., Altomonte, M., Anelli, N., Angiò, F., Annale, P., Antonacci, S., Anzilotta, R., Bano, F., Basadonna, O., Beduschi, L., Becagli, P., Bellotti, G., Blotta, C., Bruno, G., Cappuccini, A., Caramatti, S., Cariolato, M. P., Castellana, M., Castellani, L., Catania, R., Chielli, A., Chinellato, A., Ciaccia, A., Clerici, E., Cocci, A., Costanzo, G., D’Ercole, F., De Stefano, G., Decè, F., Di Cicco, N., Di Marco, A., Donati Sarti, C., Draghi, E., Dusi, G., Esposito, V., Ferraro, L., Ferretti, A., Ferri, E., Foggetti, L., Foglia, A., Fonzi, E., Frau, G., Fuoco, M. R., Furci, G., Gallo, L., Garra, V., Giannini, A., Gris, A., Iacovino, R., Interrigi, R., Joppi, R., Laner, B., La Fortezza, G., La Padula, A., Lista, M. R., Lupi, G., Maffei, D., Maggioni, G., Magnani, L., Marrazzo, E., Marcon, L., Marinò, V., Maroni, A., Martinelli, C., Mastandrea, E., Mastropierro, F., Meo, A. T., Mero, P., Minesso, E., Moschetta, V., Mosele, E., Nanni, C., Negretti, A., Nisticò, C., Orsini, A., Osti, M., Pacilli, M. C., Pennestre, C., Picerno, G., Piol, K., Pivano, L., Pizzuti, E., Poggi, L., Poidomani, I., Pozzetto, M., Presti, M. L., Ravani, R., Recalenda, V., Romagnuolo, F., Rossignoli, S., Rossin, E., Sabatella, C., Sacco, F., Sanità, F., Sansone, E., Servadei, F., Sisto, M. T., Sorio, A., Sorrentino, A., Spinelli, E., Spolaor, A., Squillacioti, A., Stella, P., Talerico, A., Todisco, C., Vadino, M., Zuliani, C., and Risk & Prevention Collaborative Group
Published: 2017
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7. Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

Author: Fernandez-Munoz, B, Rosell-Valle, C, Ferrari, D, Alba-Amador, J, Montiel, M, Campos-Cuerva, R, Lopez-Navas, L, Munoz-Escalona, M, Martin-Lopez, M, Profico, D, Blanco, M, Giorgetti, A, Gonzalez-Munoz, E, Marquez-Rivas, J, Sanchez-Pernaute, R, Fernandez-Munoz B., Rosell-Valle C., Ferrari D., Alba-Amador J., Montiel M. A., Campos-Cuerva R., Lopez-Navas L., Munoz-Escalona M., Martin-Lopez M., Profico D. C., Blanco M. F., Giorgetti A., Gonzalez-Munoz E., Marquez-Rivas J., Sanchez-Pernaute R., Fernandez-Munoz, B, Rosell-Valle, C, Ferrari, D, Alba-Amador, J, Montiel, M, Campos-Cuerva, R, Lopez-Navas, L, Munoz-Escalona, M, Martin-Lopez, M, Profico, D, Blanco, M, Giorgetti, A, Gonzalez-Munoz, E, Marquez-Rivas, J, Sanchez-Pernaute, R, Fernandez-Munoz B., Rosell-Valle C., Ferrari D., Alba-Amador J., Montiel M. A., Campos-Cuerva R., Lopez-Navas L., Munoz-Escalona M., Martin-Lopez M., Profico D. C., Blanco M. F., Giorgetti A., Gonzalez-Munoz E., Marquez-Rivas J., and Sanchez-Pernaute R.
Abstract: Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.
Published: 2020

8. Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats

Author: Zalfa, C, Rota Nodari, L, Vacchi, E, Gelati, M, Profico, D, Boido, M, Binda, E, De Filippis, L, Copetti, M, Garlatti, V, Daniele, P, Rosati, J, De Luca, A, Pinos, F, Cajola, L, Visioli, A, Mazzini, L, Vercelli, A, Svelto, M, Vescovi, A, Ferrari, D, Zalfa C., Rota Nodari L., Vacchi E., Gelati M., Profico D., Boido M., Binda E., De Filippis L., Copetti M., Garlatti V., Daniele P., Rosati J., De Luca A., Pinos F., Cajola L., Visioli A., Mazzini L., Vercelli A., Svelto M., Vescovi A. L., Ferrari D., Zalfa, C, Rota Nodari, L, Vacchi, E, Gelati, M, Profico, D, Boido, M, Binda, E, De Filippis, L, Copetti, M, Garlatti, V, Daniele, P, Rosati, J, De Luca, A, Pinos, F, Cajola, L, Visioli, A, Mazzini, L, Vercelli, A, Svelto, M, Vescovi, A, Ferrari, D, Zalfa C., Rota Nodari L., Vacchi E., Gelati M., Profico D., Boido M., Binda E., De Filippis L., Copetti M., Garlatti V., Daniele P., Rosati J., De Luca A., Pinos F., Cajola L., Visioli A., Mazzini L., Vercelli A., Svelto M., Vescovi A. L., and Ferrari D.
Abstract: Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of
Published: 2019

9. Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Author: Mazzini, L, Gelati, M, Profico, D, Soraru, G, Ferrari, D, Copetti, M, Muzi, G, Ricciolini, C, Carletti, S, Giorgi, C, Spera, C, Frondizi, D, Masiero, S, Stecco, A, Cisari, C, Bersano, E, Marchi, F, Sarnelli, M, Querin, G, Cantello, R, Petruzzelli, F, Maglione, A, Zalfa, C, Binda, E, Visioli, A, Trombetta, D, Torres, B, Bernardini, L, Gaiani, A, Massara, M, Paolucci, S, Boulis, N, Vescovi, A, Mazzini L., Gelati M., Profico D. C., Soraru G., Ferrari D., Copetti M., Muzi G., Ricciolini C., Carletti S., Giorgi C., Spera C., Frondizi D., Masiero S., Stecco A., Cisari C., Bersano E., Marchi F. D., Sarnelli M. F., Querin G., Cantello R., Petruzzelli F., Maglione A., Zalfa C., Binda E., Visioli A., Trombetta D., Torres B., Bernardini L., Gaiani A., Massara M., Paolucci S., Boulis N. M., Vescovi A. L., Mazzini, L, Gelati, M, Profico, D, Soraru, G, Ferrari, D, Copetti, M, Muzi, G, Ricciolini, C, Carletti, S, Giorgi, C, Spera, C, Frondizi, D, Masiero, S, Stecco, A, Cisari, C, Bersano, E, Marchi, F, Sarnelli, M, Querin, G, Cantello, R, Petruzzelli, F, Maglione, A, Zalfa, C, Binda, E, Visioli, A, Trombetta, D, Torres, B, Bernardini, L, Gaiani, A, Massara, M, Paolucci, S, Boulis, N, Vescovi, A, Mazzini L., Gelati M., Profico D. C., Soraru G., Ferrari D., Copetti M., Muzi G., Ricciolini C., Carletti S., Giorgi C., Spera C., Frondizi D., Masiero S., Stecco A., Cisari C., Bersano E., Marchi F. D., Sarnelli M. F., Querin G., Cantello R., Petruzzelli F., Maglione A., Zalfa C., Binda E., Visioli A., Trombetta D., Torres B., Bernardini L., Gaiani A., Massara M., Paolucci S., Boulis N. M., and Vescovi A. L.
Abstract: The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine 2019
Published: 2019

10. Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies

Author: Rosati, J, Ferrari, D, Altieri, F, Tardivo, S, Ricciolini, C, Fusilli, C, Zalfa, C, Profico, D, Pinos, F, Bernardini, L, Torres, B, Manni, I, Piaggio, G, Binda, E, Copetti, M, Lamorte, G, Mazza, T, Carella, M, Gelati, M, Valente, E, Simeone, A, Vescovi, A, Rosati, Jessica, Ferrari, Daniela, Altieri, Filomena, Tardivo, Silvia, Ricciolini, Claudia, Fusilli, Caterina, Zalfa, Cristina, Profico, Daniela C., Pinos, Francesca, Bernardini, Laura, Torres, Barbara, Manni, Isabella, Piaggio, Giulia, Binda, Elena, Copetti, Massimiliano, Lamorte, Giuseppe, Mazza, Tommaso, Carella, Massimo, Gelati, Maurizio, Valente, Enza Maria, Simeone, Antonio, Vescovi, Angelo L., Rosati, J, Ferrari, D, Altieri, F, Tardivo, S, Ricciolini, C, Fusilli, C, Zalfa, C, Profico, D, Pinos, F, Bernardini, L, Torres, B, Manni, I, Piaggio, G, Binda, E, Copetti, M, Lamorte, G, Mazza, T, Carella, M, Gelati, M, Valente, E, Simeone, A, Vescovi, A, Rosati, Jessica, Ferrari, Daniela, Altieri, Filomena, Tardivo, Silvia, Ricciolini, Claudia, Fusilli, Caterina, Zalfa, Cristina, Profico, Daniela C., Pinos, Francesca, Bernardini, Laura, Torres, Barbara, Manni, Isabella, Piaggio, Giulia, Binda, Elena, Copetti, Massimiliano, Lamorte, Giuseppe, Mazza, Tommaso, Carella, Massimo, Gelati, Maurizio, Valente, Enza Maria, Simeone, Antonio, and Vescovi, Angelo L.
Abstract: Establishing specific cell lineages from human induced pluripotent stem cells (hiPSCs) is vital for cell therapy approaches in regenerative medicine, particularly for neurodegenerative disorders. While neural precursors have been induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP standards, thus allowing clinical applications, has not been described. We generated hiNSCs by a virus-free technique, whose properties recapitulate those of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis (ALS) phase I clinical trial. Ex vivo, hiNSCs critically depend on exogenous mitogens for stable self-renewal and amplification and spontaneously differentiate into astrocytes, oligodendrocytes and neurons upon their removal. In the brain of immunodeficient mice, hiNSCs engraft and differentiate into neurons and glia, without tumour formation. These findings now warrant the establishment of clinical-grade, autologous and continuous hiNSC lines for clinical trials in neurological diseases such as Huntington’s, Parkinson’s and Alzheimer’s, among others.
Published: 2018

11. Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment

Author: Ferrari, D, Gelati, M, Profico, D, Vescovi, A, Profico, DC, Vescovi, AL, Ferrari, D, Gelati, M, Profico, D, Vescovi, A, Profico, DC, and Vescovi, AL
Abstract: Clinical trials for Parkinson’s disease, which used primary brain fetal tissue, have demonstrated that neural stem cell therapy could be suitable for neurodegenerative diseases. The use of fetal tissue presents several issues that have hampered the clinical development of this approach. In addition to the ethical concerns related to the required continuous supply of fetal specimen, the necessity to use cells from multiple fetuses in a single graft greatly compounded the problem. Cell viability and composition vary in different donors, and, further, the heterogeneity in the donor cells increased the probability of immunological rejection or contamination. An ideal cell source for cell therapy is one that is renewable, thus eliminating the need for transplantation of primary fetal tissue, and that also allows for viability, sterility, cell composition, and cell maturation to be controlled, while being inherently not tumorigenic. The availability of continuous and standardized clinical grade normal human neural cells, able to combine the plasticity of fetal tissue with an extensive proliferating capacity and functional stability, would be of paramount importance for the translation of cell therapy for central nervous system (CNS) disorders into the clinic. Here we describe a well-established protocol to produce human neural stem cells following GMP guidelines that allows us to obtain “clinical grade” cell lines.
Published: 2018

12. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

Author: Marzona, I., Avanzini, F., Lucisano, G., Tettamanti, M., Baviera, M., Nicolucci, A., Roncaglioni, M. C., Tombesi, M., Tognoni, G., Massa, E., Marrocco, W., Micalella, M., Caimi, V., Longoni, P., Franzosi, M. G., Monesi, L., Pangrazzi, I., Barlera, S., Milani, V., Nicolis, E., Casola, C., Clerici, F., Palumbo, A., Sgaroni, G., Marchioli, R., Silletta, M. G., Pioggiarella, R., Scarano, M., Marfisi, R. M., Flamminio, A., Macino, L., Ferri, B., Pera, C., Polidoro, A., Abbatino, D., Acquati, M., Addorisio, G., Adinolfi, D., Adreani, L., Agistri, M. R., Agneta, A., Agnolio, M. L., Agostini, N., Agostino, G., Airo, A., Alaimo, N., Albano, M., Albano, N., Alecci, G., Alemanno, S., Alexanian, A., Alfarano, M., Alfe, L., Alonzo, N., Alvino, S., Ancora, A., Andiloro, S., Andreatta, E., Angeli, S., Angiari, F., Angilletti, V., Annicchiarico, C., Anzivino, M., Aprea, R., Aprile, A., Aprile, E., Aprile, I., Aprile, L., Armellani, V., Arnetoli, M., Aronica, A., Autiero, V., Bacca, G., Baccalaro, A. M., Bacci, M., Baglio, G., Bagnani, M., Baiano, A., Baldari, A., Ballarini, L., Banchi, G., Bandera, R., Bandini, F., Baratella, M., Barbieri, A., Barbieri Vita, A., Bardi, M., Barlocchi, M., Baron, P., Bartoli, M., Basile, A., Basile, F., Basile, S., Battaggia, A., Battaglia, A., Bau, A., Beconcini, G., Beggio, R., Belfiore, P. A., Belicchi, M., Bellamoli, S., Bellini, C., Bellomo, M., Benetollo, C., Benetti, R., Beretta, E., Bertalero, P., Bertaso, F. G., Bertolani, U., Bettelli, G., Biagiotti, G., Bianchi, S., Bianco, G., Biccari, F., Bigioli, F., Bindi, M., Bisanti, G., Bitetti, E. M., Blasetti, M. P., Blesi, F., Boato, V., Boga, S., Boidi, E., Boldrin, G., Bollati, A., Bolzan, L., Bolzonella, S., Bonardi, P., Bonato, G. B., Bonci, M., Bonfitto, G., Bonincontro, E., Boninsegna, F., Bonissone, D., Bono, L., Bonollo, E., Borghi, M., Borioli, N., Borsatto, M., Bosco, T., Bosisio Pioltelli, M., Botarelli, C., Botassis, S., Bottini, F., Bottos, C., Bova, G., Bova, V., Bozzani, A., Bozzetto, R. M., Braga, V. T., Braglia, M., Bramati, E., Brazzoli, C., Breglia, G., Brescia, A., Briganti, D., Brigato, G., Brocchi, A., Brosio, F. A., Bruni, E., Buscaglia, E., Bussini, M. D., Bussotti, A., Buzzaccarini, F., Buzzatti, A., Caccamo, G., Cacciavillani, C., Caggiano, G., Calciano, F. P., Calderisi, M., Calienno, S., Caltagirone, P., Calzolari, I., Cammisa, M., Campanaro, M., Campanella, G. B., Campese, F., Canali, G., Candiani, D. E. L., Canepa, R., Canini, D., Canino, A., Cantoro, E. A., Capilupi, V., Capotosto, P., Cappelli, B., Capraro, G., Carafa, F. A., Carano, Q., Carcaterra, V., Carriero, D., Carrozzo, G., Cartanese, M., Casalena, M., Casarola, M., Caso, C., Casotto, M., Castaldi, F., Castegnaro, R., Castellani, G., Castri, S., Catalano, E., Catinello, N., Caturano, G., Cavallaro, R., Cavallo, A. M., Cavallo, G., Cavion, M. T., Cavirani, G., Cazzaniga, F., Cazzetta, D., Cecconi, V., Cefalo, A., Celebrano, M., Celora, A., Centonze, P., Cerati, D., Cesaretti, D., Checchia, G., Checchin, A., Cherubini, M., Chianese, L., Chiappa, A., Chiappa, M. V., Chiariello, G., Chiavini, G., Chicco, M., Chiumeo, F., Ciacciarelli, A., Ciaci, D., Ciancaglini, R., Cicale, C., Cicale, S., Cipolla, A., Ciruolo, A., Citeri, A. L., Citterio, G., Clerici, M., Coazzoli, E., Collecchia, G., Colletta, F., Colombo, I., Colorio, P., Coluccia, S., Comerio, M., Comoretto, P., Compagni, M., Conte, O., Contri, S., Contrisciani, A., Coppetti, T., Corasaniti, F., Corradi, M. T., Corsano, A., Corsini, A., Corti, N., Costantini, G., Costantino, A., Cotroneo, S., Cozzi, D., Cravello, M. G., Cristiano, E., Cucchi, R., Cusmai, L., D'Errico, G. B., D'Agostino, P., Dal Bianco, L., Dal Mutto, U., Dal Pozzo, G., Dallapiccola, P., Dallatorre, G., Dalle Molle, G., Dalloni, E., D'Aloiso, A., D'Amicis, G., Danese, R., Danieli, D., Danisi, G., D'Anna, M. A., Danti, G., D'Ascanio, S., Davidde, G., De Angeli, D., De Bastiani, R., De Battisti, A., De Bellis, A., De Berardinis, G., De Carlo, F., De Giorgi, D., De Gobbi, R., De Lorenzis, E., De Luca, P., De Martini, G., De Marzi, M., De Matteis, D., De Padova, S., De Polo, P., De Sabato, N., De Stefano, T., De Vita, M. T., De Vito, U., De Zolt, V., Debernardi, F., Del Carlo, A., Del Re, G., Del Zotti, F., D'Elia, R., Della Giovanna, P., Dell'Acqua, L., Dell'Orco, R. L., Demaria, G., Di Benedetto, M. G., Di Chiara, G., Di Corcia, V., Di Domizio, O., Di Donato, P., Di Donato, S., Di Fermo, G., Di Franco, M., Di Giovannantonio, G., Di Lascio, G., Di Lecce, G., Di Lorenzo, N., Di Maro, T., Di Mattia, Q., Di Michele, E., Di Modica, R. S., Di Murro, D., Di Noi, M. C., Di Paoli, V., Di Santi, M., Di Sanzo, A., Di Turi, C., Diazzi, A., Dileo, I., D'Ingianna, A. P., Dolci, A., Dona, G., Donato, C., Donato, P., Donini, A., Donna, M. E., Donvito, T. V., Esposito, L., Esposito, N., Evangelista, M., Faita, G., Falco, M., Falcone, D. A., Falorni, F., Fanciullacci, A., Fanton, L., Fasolo, L., Fassina, R., Fassone, A., Fatarella, P., Fedele, F., Fera, I., Fera, L., Ferioli, S., Ferlini, M. G., Ferlino, R., Ferrante, G., Ferrara, F. N., Ferrarese, M. F., Ferrari, G., Ferrari, O., Ferreri, A., Ferroni, M., Fezzi, G., Figaroli, C., Fina, M. G., Fioretta, A., Fiorucci, C., Firrincieli, R., Fischetti, M., Fischietti, G., Fiume, D. C., Flecchia, G., Forastiere, G., Fossati, B., Franceschi, P. L., Franchi, L., Franzoso, F., Frapporti, G., Frasca, G., Frisotti, A., Fumagalli, G., Fusco, D., Gabriele, P., Gabrieli, A., Gagliano, D., Galimberti, G., Galli, A., Gallicchio, N., Gallio, F., Gallipoli, T., Gallo, P., Galopin, T., Gambarelli, L., Garbin, A., Garozzo, G. M., Gasparri, R., Gastaldo, M., Gatti, E., Gazzaniga, P., Gennachi, N., Gentile, R. V., Germani, P., Gesualdi, F., Gherardi, E., Ghezzi, C., Ghidini, M. G., Ghionda, F., Giacci, L., Gialdini, D., Giampaolo, C., Giancane, R., Giannanti, A., Giannese, S., Giannini, L., Giaretta, M., Giaretta, R., Giavardi, L., Giordano, P., Giordano, E., Giordano, B., Gioria, G. M., Giugliano, R., Grassi, E. A., Greco, A., Greco, L., Grilletti, N., Grimaldi, N., Grisetti, G., Groppelli, G., Gualtieri, L., Guarducci, M., Guastella, G., Guerra, M., Guerrini, F., Guglielmini, A., Guido, A., Gulotta, P., Iacono, E., Iadarola, G., Ianiro, G., Iarussi, V., Ieluzzi, M. L., Ierardi, C., Ingaldi, F., Interlandi, S., Iocca, M., Iorno, A., Ioverno, E., Iurato, R., La Pace, L., La Piscopia, C., La Selva, R., Lafratta, M., Lamparelli, M., Lanaro, G., Lancerotto, R., Larcher, M., Lassandro, M., Lattuada, G., Laurino, P., Lefons, C., Legrottaglie, F., Lemma, A., Leone, D., Leone, F., Leso, A., Leuzzi, G., Levato, G., Libardi, L., Libralesso, N., Licini, P. I., Licursi, G., Lidonnici, F., Lillo, C., Liveri, L., Livio, A., Loiero, R. A., Loison, M., Lombardo, G., Lombardo, T., Lomunno, V., Lomuscio, S., Lonedo, A., Longo, E., Lora, L., Lotterio, A., Lucatello, L., Luongo, A., Lupoli, M., Macchia, C., Macri, G., Mafessanti, M., Maggialetti, V., Maggioni, A., Magnani, M., Maiellaro, G., Mancuso, A., Maniglio, A. R., Mannari, G. L., Manni, A., Manocchio, B., Mao, M., Marano, A., Maraone, E., Marascio, D., Marcheselli, P., Marchetto, B., Marchetto, S., Marchi, A., Marchi, G. L., Mariano, C., Marinacci, S., Marinelli, S., Marini, G., Marra, V. C., Marrali, F., Marseglia, C., Martello, G., Martino, C., Martino, G., Martino, M., Marulli, C. F., Maruzzi, G., Marzotti, A., Mascheroni, G., Mascolo, P., Masoch, G., Masone, R., Massa, L., Massafra, M., Massi, M., Massignani, D. M., Matarese, A. M., Matini, G., Mauro, R., Mazzi, M., Mazzillo, A., Mazzocato, E., Mazzoleni, N. S., Mazzone, A., Melacci, A., Mele, E., Meliota, P., Menaspa, S., Meneghello, F., Merola, G., Merone, L., Metrucci, A., Mezzina, V., Micchi, A., Michielon, A., Migliore, N., Minero, G., Minotta, F., Mirandola, C., Mistrorigo, S., Modafferi, L., Moitre, R., Mola, E., Monachese, C., Mongiardini, C., Montagna, F., Montani, M., Montemurno, I., Montolli, R., Montorsi, S., Montresor, M., Monzani, M. G., Morabito, F., Mori, G., Moro, A., Mosca, M. F., Motti, F., Muddolon, L., Mugnai, M., Muscas, F., Naimoli, F., Nanci, G., Nargi, E., Nasorri, R., Nastrini, G., Negossi, M., Negrini, A., Negroni, A., Neola, V., Niccolini, F., Niro, C. M., Nosengo, C., Novella, G., Nuti, C., Obici, F., Olita, C., Oliverio, S. S., Olivieri, I., Oriente, S., Orlando, G., Paci, C., Pagano, G., Pagliara, C., Paita, G., Paladini, G., Paladino, G., Palano, T., Palatella, A., Palermo, P., Palmisano, M., Pando, P., Panessa, P., Panigo, F., Panozzo, G., Panvini, F., Panzieri, F., Panzino, A., Panzitta, F., Paoli, N., Papagna, R., Papaleo, M. G., Papalia, G., Parisi, R., Parotti, N., Parravicini, D., Passarella, P., Pastore, G. A., Patafio, M., Pavone, P., Pedroli, W., Pedroni, M., Pelligra, G., Pellizzari, M., Penati, A., Perlot, M., Perrone, A., Perrone, G., Peruzzi, P., Peselli, C., Petracchini, L., Petrera, L., Petrone, S., Peverelli, C., Pianorsi, F., Piazza, G. P., Piazzolla, G., Picci, A., Pienabarca, G., Pietronigro, T. P., Pignocchino, P., Pilone, R., Pinto, D., Pirovano, E., Pirrotta, D., Pisante, V., Pitotto, P., Pittari, L., Piva, A., Pizzoglio, A., Plantera, O. R., Plebani, W., Plessi, S., Podrecca, D., Poerio, V., Poggiani, F., Pogliani, W., Poli, L., Poloni, F. G., Porcelli, R., Porto, S., Pranzo, L., Prevedello, C., Profeta, C., Profico, D., Punzi, A., Quaglia, G. M., Racano, M., Raccone, A., Radice, F., Raho, C. A., Raimondi, R., Raino, M., Ramponi, R., Ramunni, A., Ramunni, A. L., Ravasio, F., Ravera, M., Re Sarto, G., Rebustello, G., Regazzoli, S., Restelli, C., Rezzonico, M., Ricchiuto, F., Rigo, S., Rigon, G., Rigon, R., Rinaldi, O. V., Rinaldi, M., Risplendente, P. G., Rispoli, M., Riundi, R., Riva, M. G., Rizzi, A. L., Rizzi, D., Rizzo, L. D., Rocchi, L., Rondinone, B., Rosa, B., Rosati, F., Roselli, F., Rossetti, A., Rossetti, C., Rossi, R., Rossi, P. R., Rossi, A., Rossi, C. L., Rossitto, A., Ruffini, R., Ruffo, A., Ruggio, S., Ruo, M., Russo, B., Russo, L., Russo, R., Russo, S., Russo, U., Russo, V., Ruta, G., Sacchi, F., Sacco Botto, F., Saia, A., Salladini, G., Salmoiraghi, S., Saluzzo, F., Salvatore, C., Salvatori, E., Salvio, G., Sandri, P., Sandrini, T., Sangermano, V., Santoni, N., Saracino, A. D., Saracino, A., Sarasin, P., Sardo Infirri, C., Sarri, B., Sartori, G., Sartori, N., Sauro, C., Scaglioni, M., Scalfi, C., Scamardella, A. M., Scandale, G., Scandone, L., Scannavini, G., Scarati, R., Scardi, A., Scarpa, F. M., Scazzi, P., Schifone, A., Schiroso, G., Scigliano, G., Scilla, A., Sciortino, M., Scolaro, G., Scollo, E., Scorretti, G., Sellitti, R., Selmo, A., Selvaggio, G., Sempio, A., Seren, F., Serio, L., Serra, C., Serra, L., Siciliano, D., Sideri, A., Sighele, M., Signore, R., Siliberto, F., Silvestro, M., Simioni, G., Simmini, G., Simonato, L., Sinchetto, F., Sizzano, E., Smajato, G., Smaldone, M., Sola, G., Sordillo, L., Sovran, C. S., Spagnul, P., Spano, F., Sproviero, S., Squintani, A., Stella, L., Stilo, V., Stocchiero, B., Stornello, M. C., Stracka, G., Strada, S., Stranieri, G., Stucci, N., Stufano, N., Suppa, A., Susca, V. 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A., Zambon, N., Zammarrelli, A., Zanaboni, A., Zane, D., Zanetti, B., Zanibellato, R., Zappetti, M., Zappone, P., Zerilli, G., Zirino, V., Zoccali, R., Zuin, F., Altomonte, M., Anelli, N., Angio, F., Annale, P., Antonacci, S., Anzilotta, R., Bano, F., Basadonna, O., Beduschi, L., Becagli, P., Bellotti, G., Blotta, C., Bruno, G., Cappuccini, A., Caramatti, S., Cariolato, M. P., Castellana, M., Castellani, L., Catania, R., Chielli, A., Chinellato, A., Ciaccia, A., Clerici, E., Cocci, A., Costanzo, G., D'Ercole, F., De Stefano, G., Dece, F., Di Cicco, N., Di Marco, A., Donati Sarti, C., Draghi, E., Dusi, G., Esposito, V., Ferraro, L., Ferretti, A., Ferri, E., Foggetti, L., Foglia, A., Fonzi, E., Frau, G., Fuoco, M. R., Furci, G., Gallo, L., Garra, V., Giannini, A., Gris, A., Iacovino, R., Interrigi, R., Joppi, R., Laner, B., La Fortezza, G., La Padula, A., Lista, M. R., Lupi, G., Maffei, D., Maggioni, G., Magnani, L., Marrazzo, E., Marcon, L., Marino, V., Maroni, A., Martinelli, C., Mastandrea, E., Mastropierro, F., Meo, A. T., Mero, P., Minesso, E., Moschetta, V., Mosele, E., Nanni, C., Negretti, A., Nistico, C., Orsini, A., Osti, M., Pacilli, M. C., Pennestre, C., Picerno, G., Piol, K., Pivano, L., Pizzuti, E., Poggi, L., Poidomani, I., Pozzetto, M., Presti, M. L., Ravani, R., Recalenda, V., Romagnuolo, F., Rossignoli, S., Rossin, E., Sabatella, C., Sacco, F., Sanita, F., Sansone, E., Servadei, F., Sisto, M. T., Sorio, A., Sorrentino, A., Spinelli, E., Spolaor, A., Squillacioti, A., Stella, P., Talerico, A., Todisco, C., Vadino, M., and Zuliani, C.
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Overweight, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Prediction model, Internal medicine, Diabetes mellitus, Internal Medicine, Diabetes Mellitus, Medicine, Humans, Multicenter Studies as Topic, Myocardial infarction, Risk factor, education, Stroke, Aged, Randomized Controlled Trials as Topic, education.field_of_study, Lifestyle habits, business.industry, Major cardiovascular events, Atrial fibrillation, General Medicine, Middle Aged, medicine.disease, Cardiovascular Diseases, Heart failure, Physical therapy, Female, medicine.symptom, business, Diabetic Angiopathies
Abstract: To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention. People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk. In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women. In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.
Published: 2016

13. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?

Author: Atassi, N, Beghi, E, Blanquer, M, Boulis, N, Cantello, R, Caponnetto, C, Chiò, A, Dunnett, S, Feldman, E, Vescovi, A, Mazzini, L, Bendotti, C, Bersano, E, Brajkovic, S, Car, P, De Marchi, F, Fantozzi, R, Follenzi, A, Gelati, M, Giorgi, C, Grilli, M, Guenzi, P, La Bella, V, Mancardi, G, Panzarasa, G, Poloni, M, Profico, D, Silani, V, Sorarù, G, Spataro, R, Stecco, A, Vercelli, A, Boulis, NM, Dunnett, SB, Feldman, EL, Mancardi, GL, Atassi, N, Beghi, E, Blanquer, M, Boulis, N, Cantello, R, Caponnetto, C, Chiò, A, Dunnett, S, Feldman, E, Vescovi, A, Mazzini, L, Bendotti, C, Bersano, E, Brajkovic, S, Car, P, De Marchi, F, Fantozzi, R, Follenzi, A, Gelati, M, Giorgi, C, Grilli, M, Guenzi, P, La Bella, V, Mancardi, G, Panzarasa, G, Poloni, M, Profico, D, Silani, V, Sorarù, G, Spataro, R, Stecco, A, Vercelli, A, Boulis, NM, Dunnett, SB, Feldman, EL, and Mancardi, GL
Abstract: Intraspinal stem cell (SC) transplantation represents a new therapeutic approach for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable difficulties in designing future efficacy trials, some related to the field of ALS and some that are specific to SCs or the mode of delivery. In October 2015, the most controversial points on SC transplantation were addressed during an international workshop intended to bring together international SC and ALS researchers in a public discussion on a topic for which expertise is limited. During the meeting, a discussion was started on the basic structure of the ideal clinical trial testing the efficacy and safety of SC transplantation. The current document includes a number of consensus points reflecting the design of phase II/III clinical trials.
Published: 2016

14. N-3 fatty acids in patients with multiple cardiovascular risk factors

Author: Roncaglioni, Maria Carla, Avanzini, Fausto, Barlera, Simona, Marzona, Irene, Milani, Valentina, Tombesi, Massimo, Caimi, Vittorio, Longoni, Paolo, Silletta, Maria Giuseppina, Tognoni, Gianni, Marchioli, Avanzini F, Roberto., Caimi, V, Longoni, P, Marchioli, R, Roncaglioni, Mc, Silletta, Mg, Tognoni, G, Tombesi, M, Barlera, S, Milani, V, Nicolis, Eb, Casola, C, Marzona, I, Massa, E, Marrocco, W, Micalella, M, Avanzini, F, Franzosi, Mg, Geraci, E, Giansiracusa, N, Rocchetti, L, Decarli, A, Satolli, R, Alli, C, Beghi, E, Bertele', V, Volpi, A, Baviera, M, Monesi, L, Pangrazzi, I, Nicolis, E, Clerici, F, Palumbo, A, Sgaroni, G, Pioggiarella, R, Scarano, M, Marfisi, Rm, Flamminio, A, Macino, L, Ferri, B, Pera, C, Polidoro, A, Abbatino, D, Acquati, M, Addorisio, G, Adinolfi, D, Adreani, L, Agistri, Mr, Agneta, A, Agnolio, Ml, Agostini, N, Agostino, G, Airò, A, Alaimo, N, Albano, M, Albano, N, Alecci, G, Alemanno, S, Alexanian, A, Alfarano, M, Alfè, L, Alonzo, N, Alvino, S, Ancora, A, Andiloro, S, Andreatta, E, Angeli, S, Angiari, F, Angilletti, V, Annicchiarico, C, Anzivino, M, Aprea, R, Aprile, A, Aprile, E, Aprile, I, Aprile, L, Armellani, V, Arnetoli, M, Aronica, A, Autiero, V, Bacca, G, Baccalaro, Am, Bacci, M, Baglio, G, Bagnani, M, Baiano, A, Baldari, A, Ballarini, L, Banchi, G, Bandera, R, Bandini, F, Baratella, M, Barbieri, A, Barbieri Vita, A, Bardi, M, Barlocchi, M, Baron, P, Bartoli, M, Basile, A, Basile, F, Basile, S, Battaggia, A, Battaglia, A, Baù, A, Beconcini, G, Beggio, R, Belfiore, Pa, Belicchi, M, Bellamoli, S, Bellini, C, Bellomo, M, Benetollo, C, Benetti, R, Beretta, E, Bertalero, P, Bertaso, Fg, Bertolani, U, Bettelli, G, Biagiotti, G, Bianchi, S, Bianco, G, Biccari, F, Bigioli, F, Bindi, M, Bisanti, G, Bitetti, Em, Blasetti, Mp, Blesi, F, Boato, V, Boga, S, Boidi, E, Boldrin, G, Bollati, A, Bolzan, L, Bolzonella, S, Bonardi, P, Bonato, Gb, Bonci, M, Bonfitto, G, Bonincontro, E, Boninsegna, F, Bonissone, D, Bono, L, Bonollo, E, Borghi, M, Borioli, N, Borsatto, M, Bosco, T, Bosisio Pioltelli, M, Botarelli, C, Botassis, S, Bottini, F, Bottos, C, Bova, G, Bova, V, Bozzani, A, Bozzetto, Rm, Braga, Vt, Braglia, M, Bramati, E, Brazzoli, C, Breglia, G, Brescia, A, Briganti, D, Brigato, G, Brocchi, A, Brosio, Fa, Bruni, E, Buscaglia, E, Bussini, Md, Bussotti, A, Buzzaccarini, F, Buzzatti, A, Caccamo, G, Cacciavillani, C, Caggiano, G, Calciano, Fp, Calderisi, M, Calienno, S, Caltagirone, P, Calzolari, I, Cammisa, M, Campanaro, M, Campanella, Gb, Campese, F, Canali, G, Candiani, De, Canepa, R, Canini, D, Canino, A, Cantoro, Ea, Capilupi, V, Capotosto, P, Cappelli, B, Capraro, G, Carafa, Fa, Carano, Q, Carcaterra, V, Carriero, D, Carrozzo, G, Cartanese, M, Casalena, M, Casarola, M, Caso, C, Casotto, M, Castaldi, F, Castegnaro, R, Castellani, G, Castri, S, Catalano, E, Catinello, N, Caturano, G, Cavallaro, R, Cavallo, Am, Cavallo, G, Cavion, Mt, Cavirani, G, Cazzaniga, F, Cazzetta, D, Cecconi, V, Cefalo, A, Celebrano, M, Celora, A, Centonze, P, Cerati, D, Cesaretti, D, Checchia, G, Checchin, A, Cherubini, M, Chianese, L, Chiappa, A, Chiappa, Mv, Chiariello, G, Chiavini, G, Chicco, M, Chiumeo, F, Ciacciarelli, A, Ciaci, D, Ciancaglini, R, Cicale, C, Cicale, S, Cipolla, A, Ciruolo, A, Citeri, Al, Citterio, G, Clerici, M, Coazzoli, E, Collecchia, G, Colletta, F, Colombo, I, Colorio, P, Coluccia, S, Comerio, M, Comoretto, P, Compagni, M, Conte, O, Contri, S, Contrisciani, A, Coppetti, T, Corasaniti, F, Corradi, Mt, Corsano, A, Corsini, A, Corti, N, Costantini, G, Costantino, A, Cotroneo, S, Cozzi, D, Cravello, Mg, Cristiano, E, Cucchi, R, Cusmai, L, D' Errico GB, D'Agostino, P, Dal Bianco, L, Dal Mutto, U, Dal Pozzo, G, Dallapiccola, P, Dallatorre, G, Dalle Molle, G, Dalloni, E, D'Aloiso, A, D'Amicis, G, Danese, R, Danieli, D, Danisi, G, D'Anna, Ma, Danti, G, D'Ascanio, S, Davidde, G, De Angeli, D, De Bastiani, R, De Battisti, A, De Bellis, A, De Berardinis, G, De Carlo, F, De Giorgi, D, De Gobbi, R, De Lorenzis, E, De Luca, P, De Martini, G, De Marzi, M, De Matteis, D, De Padova, S, De Polo, P, De Sabato, N, De Stefano, T, De Vita MT, De Vita, U, De Zolt, V, Debernardi, F, Del Carlo, A, Del Re, G, Del Zotti, F, D'Elia, R, Della Giovanna, P, Dell'Acqua, L, Dell'Orco, Rl, Demaria, G, Di Benedetto MG, Di Chiara, G, Di Corcia, V, Di Domizio, O, Di Donato, P, Di Donato, S, Di Fermo, G, Di Franco, M, Di Giovannantonio, G, Di Lascio, G, Di Lecce, G, Di Lorenzo, N, Di Maro, T, Di Mattia, Q, Di Michele, E, Di Modica RS, Di Murro, D, Di Noi MC, Di Paoli, V, Di Santi, M, Di Sanzo, A, Di Turi, C, Diazzi, A, Dileo, I, D'Ingianna, Ap, Dolci, A, Donà, G, Donato, C, Donato, P, Donini, A, Donna, Me, Donvito, Tv, Esposito, L, Esposito, N, Evangelista, M, Faita, G, Falco, M, Falcone, Da, Falorni, F, Fanciullacci, A, Fanton, L, Fasolo, L, Fassina, R, Fassone, A, Fatarella, P, Fedele, F, Fera, I, Fera, L, Ferioli, S, Ferlini, Mg, Ferlino, R, Ferrante, G, Ferrara, Fn, Ferrarese, Mf, Ferrari, G, Ferrari, O, Ferreri, A, Ferroni, M, Fezzi, G, Figaroli, C, Fina, Mg, Fioretta, A, Fiorucci, C, Firrincieli, R, Fischetti, M, Fischietti, G, Fiume, Dc, Flecchia, G, Forastiere, G, Fossati, B, Franceschi, Pl, Franchi, L, Franzoso, F, Frapporti, G, Frasca, G, Frisotti, A, Fumagalli, G, Fusco, D, Gabriele, P, Gabrieli, A, Gagliano, D, Galimberti, G, Galli, A, Gallicchio, N, Gallio, F, Gallipoli, T, Gallo, P, Galopin, T, Gambarelli, L, Garbin, A, Garozzo, Gm, Gasparri, R, Gastaldo, M, Gatti, E, Gazzaniga, P, Gennachi, N, Gentile, Rv, Germani, P, Gesualdi, F, Gherardi, E, Ghezzi, C, Ghidini, Mg, Ghionda, F, Giacci, L, Gialdini, D, Giampaolo, C, Giancane, R, Giannanti, A, Giannese, S, Giannini, L, Giaretta, M, Giaretta, R, Giavardi, L, Giordano, P, Giordano, E, Giordano, B, Gioria, Gm, Giugliano, R, Grassi, Ea, Greco, A, Greco, L, Grilletti, N, Grimaldi, N, Grisetti, G, Groppelli, G, Gualtieri, L, Guarducci, M, Guastella, G, Guerra, M, Guerrini, F, Guglielmini, A, Guido, A, Gulotta, P, Iacono, E, Iadarola, G, Ianiro, G, Iarussi, V, Ieluzzi, Ml, Ierardi, C, Ingaldi, F, Interlandi, S, Iocca, M, Iorno, A, Ioverno, E, Iurato, R, La Pace, L, La Piscopia, C, La Selva, R, Lafratta, M, Lamparelli, M, Lanaro, G, Lancerotto, R, Larcher, M, Lassandro, M, Lattuada, G, Laurino, P, Lefons, C, Legrottaglie, F, Lemma, A, Leone, D, Leone, F, Leso, A, Leuzzi, G, Levato, G, Libardi, L, Libralesso, N, Licini, Pi, Licursi, G, Lidonnici, F, Lillo, C, Liveri, L, Livio, A, Loiero, Ra, Loison, M, Lombardo, G, Lombardo, T, Lomunno, V, Lomuscio, S, Lonedo, A, Longo, E, Lora, L, Lotterio, A, Lucatello, L, Luongo, A, Lupoli, M, Macchia, C, Macri, G, Mafessanti, M, Maggialetti, V, Maggioni, A, Magnani, M, Maiellaro, G, Mancuso, A, Maniglio, Ar, Mannari, Gl, Manni, A, Manocchio, B, Mao, M, Maranò, A, Maraone, E, Marascio, D, Marcheselli, P, Marchetto, B, Marchetto, S, Marchi, A, Marchi, Gl, Mariano, C, Marinacci, S, Marinelli, S, Marini, G, Marra, Vc, Marrali, F, Marseglia, C, Martello, G, Martino, C, Martino, G, Martino, M, Marulli, Cf, Maruzzi, G, Marzotti, A, Mascheroni, G, Mascolo, P, Masoch, G, Masone, R, Massa, L, Massafra, M, Massi, M, Massignani, Dm, Matarese, Am, Matini, G, Mauro, R, Mazzi, M, Mazzillo, A, Mazzocato, E, Mazzoleni, Ns, Mazzone, A, Melacci, A, Mele, E, Meliota, P, Menaspà, S, Meneghello, F, Merola, G, Merone, L, Metrucci, A, Mezzina, V, Micchi, A, Michielon, A, Migliore, N, Minero, G, Minotta, F, Mirandola, C, Mistrorigo, S, Modafferi, L, Moitre, R, Mola, E, Monachese, C, Mongiardini, C, Montagna, F, Montani, M, Montemurno, I, Montolli, R, Montorsi, S, Montresor, M, Monzani, Mg, Morabito, F, Mori, G, Moro, A, Mosca, Mf, Motti, F, Muddolon, L, Mugnai, M, Muscas, F, Naimoli, F, Nanci, G, Nargi, E, Nasorri, R, Nastrini, G, Negossi, M, Negrini, A, Negroni, A, Neola, V, Niccolini, F, Niro, Cm, Nosengo, C, Novella, G, Nuti, C, Obici, F, Olita, C, Oliverio, Ss, Olivieri, I, Oriente, S, Orlando, G, Paci, C, Pagano, G, Pagliara, C, Paita, G, Paladini, G, Paladino, G, Palano, T, Palatella, A, Palermo, P, Palmisano, M, Pando, P, Panessa, P, Panigo, F, Panozzo, G, Panvini, F, Panzieri, F, Panzino, A, Panzitta, F, Paoli, N, Papagna, R, Papaleo, Mg, Papalia, G, Parisi, R, Parotti, N, Parravicini, D, Passarella, P, Pastore, Ga, Patafio, M, Pavone, P, Pedroli, W, Pedroni, M, Pelligra, G, Pellizzari, M, Penati, A, Perlot, M, Perrone, A, Perrone, G, Peruzzi, P, Peselli, C, Petracchini, L, Petrera, L, Petrone, S, Peverelli, C, Pianorsi, F, Piazza, Gp, Piazzolla, G, Picci, A, Pienabarca, G, Pietronigro, Tp, Pignocchino, P, Pilone, R, Pinto, D, Pirovano, E, Pirrotta, D, Pisante, V, Pitotto, P, Pittari, L, Piva, A, Pizzoglio, A, Plantera, Or, Plebani, W, Plessi, S, Podrecca, D, Poerio, V, Poggiani, F, Pogliani, W, Poli, L, Poloni, Fg, Porcelli, R, Porto, S, Pranzo, L, Prevedello, C, Profeta, C, Profico, D, Punzi, A, Quaglia, Gm, Racano, M, Raccone, A, Radice, F, Raho, Ca, Raimondi, R, Rainò, M, Ramponi, R, Ramunni, A, Ramunni, Al, Ravasio, F, Ravera, M, Re Sartò, G, Rebustello, G, Regazzoli, S, Restelli, C, Rezzonico, M, Ricchiuto, F, Rigo, S, Rigon, G, Rigon, R, Rinaldi, Ov, Rinaldi, M, Risplendente, Pg, Rispoli, M, Riundi, R, Riva, Mg, Rizzi, Al, Rizzi, D, Rizzo, Ld, Rocchi, L, Rondinone, B, Rosa, B, Rosati, F, Roselli, F, Rossetti, A, Rossetti, C, Rossi, R, Rossi, Pr, Rossi, A, Rossi, Cl, Rossitto, A, Ruffini, R, Ruffo, A, Ruggio, S, Ruo, M, Russo, B, Russo, L, Russo, R, Russo, S, Russo, U, Russo, V, Ruta, G, Sacchi, F, Sacco Botto, F, Saia, A, Salladini, G, Salmoiraghi, S, Saluzzo, F, Salvatore, C, Salvatori, E, Salvio, G, Sandri, P, Sandrini, T, Sangermano, V, Santoni, N, Saracino, Ad, Saracino, A, Sarasin, P, Sardo Infirri, C, Sarrì, B, Sartori, G, Sartori, N, Sauro, C, Scaglioni, M, Scalfi, C, Scamardella, Am, Scandale, G, Scandone, L, Scannavini, G, Scarati, R, Scardi, A, Scarpa, Fm, Scazzi, P, Schifone, A, Schirosa, G, Scigliano, G, Scilla, A, Sciortino, M, Scolaro, G, Scollo, E, Scorretti, G, Sellitti, R, Selmo, A, Selvaggio, G, Sempio, A, Seren, F, Serio, L, Serra, C, Serra, L, Siciliano, D, Sideri, A, Sighele, M, Signore, R, Siliberto, F, Silvestro, M, Simioni, G, Simmini, G, Simonato, L, Sinchetto, F, Sizzano, E, Smajato, G, Smaldone, M, Sola, G, Sordillo, L, Sovran, Cs, Spagnul, P, Spanò, F, Sproviero, S, Squintani, A, Stella, L, Stilo, V, Stocchiero, B, Stornello, Mc, Stracka, G, Strada, S, Stranieri, G, Stucci, N, Stufano, N, Suppa, A, Susca, Vg, Sutti, M, Taddei, M, Tagliabue, E, Tagliente, G, Talato, F, Talerico, P, Talia, R, Taranto, R, Tartaglia, M, Tauro, N, Tedesco, A, Tieri, P, Tirelli, M, Tocci, L, Todesco, P, Tognolo, M, Tomba, A, Tonello, P, Tonon, R, Toscano, L, Tosi, A, Tosi, G, Toso, S, Travaglio, P, Tremul, L, Tresso, C, Triacchini, P, Triggiano, L, Trigilio, A, Trimeloni, J, Tripicchio, G, Tritto, Gs, Trono, F, Trotta, E, Trotta, G, Tubertini, A, Turri, C, Turri, L, Tuttolani, Mp, Urago, M, Ursini, G, Valcanover, F, Valente, L, Valenti, M, Valentini, F, Vallone, G, Valz, P, Valzano, L, Vanin, V, Vatteroni, M, Vegetti, L, Vendrame, D, Veramonti, I, Veronelli, G, Vesco, A, Vicariotto, G, Vignale, G, Villa, Pl, Vinciguerra, R, Visco, A, Visentin, G, Visonà, E, Vitali, E, Vitali, S, Vitti, F, Volpone, Da, Zambon, N, Zammarrelli, A, Zanaboni, A, Zane, D, Zanetti, B, Zanibellato, R, Zappetti, M, Zappone, P, Zerilli, G, Zirino, V, Zoccali, R, Zuin, F, Altomonte, M, Anelli, N, Angiò, F, Annale, P, Antonacci, S, Anzilotta, R, Bano, F, Basadonna, O, Beduschi, L, Becagli, P, Bellotti, G, Blotta, C, Bruno, G, Cappuccini, A, Caramatti, S, Cariolato, Mp, Castellana, M, Castellani, L, Catania, R, Chielli, A, Chinellato, A, Ciaccia, A, Clerici, E, Cocci, A, Costanzo, G, D'Ercole, F, De Stefano, G, Decè, F, Di Cicco, N, Di Marco, A, Donati Sarti, C, Draghi, E, Dusi, G, Esposito, V, Ferraro, L, Ferretti, A, Ferri, E, Foggetti, L, Foglia, A, Fonzi, E, Frau, G, Fuoco, Mr, Furci, G, Gallo, L, Garra, V, Giannini, A, Gris, A, Iacovino, R, Interrigi, R, Joppi, R, Laner, B, La Fortezza, G, La Padula, A, Lista, Mr, Lupi, G, Maffei, D, Maggioni, G, Magnani, L, Marrazzo, E, Marcon, L, Marinò, V, Maroni, A, Martinelli, C, Mastandrea, E, Mastropierro, F, Meo, At, Mero, P, Minesso, E, Moschetta, V, Mosele, E, Nanni, C, Negretti, A, Nisticò, C, Orsini, A, Osti, M, Pacilli, Mc, Pennestre, C, Picerno, G, Piol, K, Pivano, L, Pizzuti, E, Poggi, L, Poidomani, I, Pozzetto, M, Presti, Ml, Ravani, R, Recalenda, V, Romagnuolo, F, Rossignoli, S, Rossin, E, Sabatella, C, Sacco, F, Sanità, F, Sansone, E, Servadei, F, Sisto, Mt, Sorio, A, Sorrentino, A, Spinelli, E, Spolaor, A, Squillacioti, A, Stella, P, Talerico, A, Todisco, C, Vadino, M, and Zuliani, C.
Subjects: Male, medicine.medical_specialty, General Practice, Kaplan-Meier Estimate, Placebo, Double-Blind Method, Risk Factors, Internal medicine, Fatty Acids, Omega-3, Clinical endpoint, medicine, Humans, Myocardial infarction, Treatment Failure, Aged, Proportional Hazards Models, chemistry.chemical_classification, Omega-3, business.industry, Proportional hazards model, Medicine (all), Hazard ratio, Fatty Acids, General Medicine, Middle Aged, medicine.disease, Hospitalization, Primary Prevention, chemistry, Cardiovascular Diseases, Heart failure, Cohort, Female, business, Polyunsaturated fatty acid
Abstract: Background Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. Methods In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes. Results Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points. Conclusions In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Societa Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).
Published: 2013

15. Human neural stem cell transplantation in ALS: Initial results from a phase I trial

Author: Mazzini, L, Gelati, M, Profico, D, Sgaravizzi, G, Projetti Pensi, M, Muzi, G, Ricciolini, C, Rota, N, L, Carletti, S, Giorgi, C, Spera, C, Domenico, F, Bersano, E, Petruzzelli, F, Cisari, C, Maglione, A, Sarnelli, M, Stecco, A, Querin, G, Masiero, S, Cantello, R, Ferrari, D, Zalfa, M, Binda, E, Visioli, A, Trombetta, D, Novelli, A, Torres, B, Bernardini, L, Carriero, A, Prandi, P, Servo, S, Cerino, A, Cima, V, Gaiani, A, Nasuelli, N, Massara, M, Glass, J, Sorarù, G, Boulis, N, Vescovi, A, Profico, DC, Muzi G, Rota Nodari, Sarnelli, MF, FERRARI, DANIELA, ZALFA, MARIA CRISTINA, Boulis, NM, VESCOVI, ANGELO LUIGI, Mazzini, L, Gelati, M, Profico, D, Sgaravizzi, G, Projetti Pensi, M, Muzi, G, Ricciolini, C, Rota, N, L, Carletti, S, Giorgi, C, Spera, C, Domenico, F, Bersano, E, Petruzzelli, F, Cisari, C, Maglione, A, Sarnelli, M, Stecco, A, Querin, G, Masiero, S, Cantello, R, Ferrari, D, Zalfa, M, Binda, E, Visioli, A, Trombetta, D, Novelli, A, Torres, B, Bernardini, L, Carriero, A, Prandi, P, Servo, S, Cerino, A, Cima, V, Gaiani, A, Nasuelli, N, Massara, M, Glass, J, Sorarù, G, Boulis, N, Vescovi, A, Profico, DC, Muzi G, Rota Nodari, Sarnelli, MF, FERRARI, DANIELA, ZALFA, MARIA CRISTINA, Boulis, NM, and VESCOVI, ANGELO LUIGI
Abstract: Background: We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board. Methods: Six non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials. Results: No increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease. Conclusions: We describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material.
Published: 2015

16. Culturing and expansion of 'clinical grade' precursors cells from the fetal human central nervous system

Author: Reynolds, BA, Deleyrolle, LP, Gelati, M, Profico, D, Projetti Pensi, M, Muzi, G, Sgaravizzi, G, Vescovi, A, VESCOVI, ANGELO LUIGI, Reynolds, BA, Deleyrolle, LP, Gelati, M, Profico, D, Projetti Pensi, M, Muzi, G, Sgaravizzi, G, Vescovi, A, and VESCOVI, ANGELO LUIGI
Abstract: NSCs have been demonstrated to be very useful in grafts into the mammalian central nervous system to investigate the exploitation of NSC for the therapy of neurodegenerative disorders in animal models of neurodegenerative diseases. To push cell therapy in CNS on stage of clinical application, it is necessary to establish a continuous and standardized, clinical grade (i.e., produced following the good manufacturing practice guidelines) human neural stem cell lines. In this chapter, we illustrate some of the protocols routinely used into our GMP cell bank for the production of "clinical grade" human neural stem cell lines. © Springer Science+Business Media New York 2013.
Published: 2013

17. Human Neural Stem Cell-Based Drug Product: Clinical and Nonclinical Characterization

Author: Daniela Celeste Profico, Maurizio Gelati, Daniela Ferrari, Giada Sgaravizzi, Claudia Ricciolini, Massimo Projetti Pensi, Gianmarco Muzi, Laura Cajola, Massimiliano Copetti, Emilio Ciusani, Raffaele Pugliese, Fabrizio Gelain, Angelo Luigi Vescovi, Profico, D, Gelati, M, Ferrari, D, Sgaravizzi, G, Ricciolini, C, Projetti Pensi, M, Muzi, G, Cajola, L, Copetti, M, Ciusani, E, Pugliese, R, Gelain, F, and Vescovi, A
Subjects: Cryopreservation, standardization, GMP, Organic Chemistry, Amyotrophic Lateral Sclerosis, Reproducibility of Results, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, neural stem cell, Neural Stem Cells, ATMP production, Humans, Physical and Theoretical Chemistry, quality control, Molecular Biology, Spectroscopy
Abstract: Translation of cell therapies into clinical practice requires the adoption of robust production protocols in order to optimize and standardize the manufacture and cryopreservation of cells, in compliance with good manufacturing practice regulations. Between 2012 and 2020, we conducted two phase I clinical trials (EudraCT 2009-014484-39, EudraCT 2015-004855-37) on amyotrophic lateral sclerosis secondary progressive multiple sclerosis patients, respectively, treating them with human neural stem cells. Our production process of a hNSC-based medicinal product is the first to use brain tissue samples extracted from fetuses that died in spontaneous abortion or miscarriage. It consists of selection, isolation and expansion of hNSCs and ends with the final pharmaceutical formulation tailored to a specific patient, in compliance with the approved clinical protocol. The cells used in these clinical trials were analyzed in order to confirm their microbiological safety; each batch was also tested to assess identity, potency and safety through morphological and functional assays. Preclinical, clinical and in vitro nonclinical data have proved that our cells are safe and stable, and that the production process can provide a high level of reproducibility of the cultures. Here, we describe the quality control strategy for the characterization of the hNSCs used in the above-mentioned clinical trials.
Published: 2022

18. Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

Author: Manuel Francisco Blanco, Daniela Celeste Profico, Elena González-Muñoz, Beatriz Fernández-Muñoz, Miguel Ángel Montiel, Cristina Rosell-Valle, María Muñoz-Escalona, Rosario Sanchez-Pernaute, María Martín-López, Julia Alba-Amador, Rafael Campos-Cuerva, Javier Márquez-Rivas, Daniela Ferrari, Alessandra Giorgetti, Luis Lopez‐Navas, Fernandez-Munoz, B, Rosell-Valle, C, Ferrari, D, Alba-Amador, J, Montiel, M, Campos-Cuerva, R, Lopez-Navas, L, Munoz-Escalona, M, Martin-Lopez, M, Profico, D, Blanco, M, Giorgetti, A, Gonzalez-Munoz, E, Marquez-Rivas, J, Sanchez-Pernaute, R, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, [Fernández-Muñoz,B, Rosell-Valle,C, Alba-Amador,J, Montiel,MÁ, Campos-Cuerva,R, Muñoz-Escalona,M, Martín-López,M, Blanco,MF] Unidad de Producción y Reprogramación Celular (UPRC), Red Andaluza para el diseño y traslación de Terapias Avanzadas, Sevilla, Spain. [Fernández-Muñoz,B, Márquez-Rivas,J] Grupo de Neurociencia aplicada, Instituto de Biomedicina de Sevilla, Sevilla, Spain. [Ferrari,D] Department of Biotechnology and Biosciences, University Milan-Bicocca, Milan, Italy. [Campos-Cuerva,R] Centro de Transfusiones, Tejidos y Células de Sevilla (CTTS), Sevilla, Spain. [Lopez-Navas,L, Sanchez-Pernaute,R] Departamento de Preclínica, Red Andaluza de Diseño y Traslación de Terapias Avanzadas, Sevilla, Spain. [Profico,DC] Fondazione IRCCS Casa Sollievo della Sofferenza, Production Unit of Advanced Therapies (UPTA), San Giovanni Rotondo, Italy. [Giorgetti,A] Regenerative Medicine Program, Bellvitge Biomedical Research Institute (IDIBELL), Program for Translation of Regenerative Medicine in Catalonia (P-CMRC), Barcelona, Spain. [González-Muñoz,E] Department of Cell Biology, Genetics and Physiology, University of Málaga, Málaga, Spain. [González-Muñoz,E] Department of Regenerative Nanomedicine, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain. [González-Muñoz,E] Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Carlos III Health Institute (ISCIII), Spain. [Márquez-Rivas,J] Neurosurgery Department, Hospital Virgen del Rocío, Sevilla, Spain., and This work was supported by research funds from the Andalusian Consejería de Salud to the Red Andaluza de Diseño y Traslación de Terapias Avanzadas with contribution from the COST Action CA16122 for STSM and networking. AG is supported by Ramon y Cajal Program (RyC-2013-13221), MINECO(SAF2016-80205-R) and CERCA Pro gram/Generalitat de Catalunya.
Subjects: 0301 basic medicine, Male, Neurobiologia del desenvolupament, Pathology, Premature infant, Infants prematurs, neural stem cell, 0302 clinical medicine, Cerebrospinal fluid, Neural Stem Cells, Tissue‐specific Progenitor and Stem Cells, Organisms::Eukaryota::Animals [Medical Subject Headings], AC133 Antigen, Developmental neurobiology, Hemorragia cerebral intraventricular, Anatomy::Cells::Stem Cells::Neural Stem Cells [Medical Subject Headings], lcsh:R5-920, lcsh:Cytology, Premature infants, Líquido cefalorraquídeo, Neurogenesis, Gene Expression Regulation, Developmental, General Medicine, Human brain, Recién nacido prematuro, Neural stem cell, premature infant, Anatomy::Fluids and Secretions::Body Fluids::Extracellular Fluid::Cerebrospinal Fluid [Medical Subject Headings], Persons::Persons::Age Groups::Infant::Infant, Newborn::Infant, Premature [Medical Subject Headings], Intraventricular hemorrhage, medicine.anatomical_structure, Centro germinal, Female, lcsh:Medicine (General), Infant, Premature, medicine.medical_specialty, neurogenesi, Mice, Nude, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Developmental [Medical Subject Headings], intraventricular hemorrhage, cerebrospinal fluid, 03 medical and health sciences, medicine, Animals, lcsh:QH573-671, Cerebral Hemorrhage, Células madre nerviosas, business.industry, Germinal zone, germinal zone, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage [Medical Subject Headings], BIO/13 - BIOLOGIA APPLICATA, Líquid cefalorraquidi, Endoscopy, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Nude [Medical Subject Headings], Cell Biology, medicine.disease, Transplantation, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cell culture, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Surgical::Endoscopy [Medical Subject Headings], Forebrain, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology., Germinal zone neural stem cells (Gz‐NSC) are isolated from the hemorrhagic cerebrospinal fluid of preterm infants with severe intraventricular hemorrhage. These cells express ventral and posterior forebrain markers, can be differentiated and do not cause tumors. Gz‐NSC represent a valuable tool for the development of new cell therapies and the study of human Gz biology.
Published: 2020

19. Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats

Author: Maria Svelto, Alberto Visioli, Daniela Celeste Profico, Laura Cajola, Massimiliano Copetti, Letizia Mazzini, Francesca Pinos, Jessica Rosati, Cristina Zalfa, Elena Binda, Laura Rota Nodari, Paola Daniele, Alessandro De Luca, Lidia De Filippis, Marina Boido, Valentina Garlatti, Angelo L. Vescovi, Daniela Ferrari, Elena Vacchi, Maurizio Gelati, Alessandro Vercelli, Zalfa, C, Rota Nodari, L, Vacchi, E, Gelati, M, Profico, D, Boido, M, Binda, E, De Filippis, L, Copetti, M, Garlatti, V, Daniele, P, Rosati, J, De Luca, A, Pinos, F, Cajola, L, Visioli, A, Mazzini, L, Vercelli, A, Svelto, M, Vescovi, A, and Ferrari, D
Subjects: Male, 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, Cell Survival, Neurogenesis, medicine.medical_treatment, Immunology, SOD1, Kaplan-Meier Estimate, hNSCs transplantation Amyotrophic Lateral Sclerosis, transgenic animal model, terapeutic mechanisms of stem cells, differentiation mechanisms of stem cells, neural stem cells, SOD1, mechanisms of ALS progression, neuroinflammation mechanisms, Article, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Animals, Humans, Medicine, lcsh:QH573-671, Amyotrophic lateral sclerosis, Neuroinflammation, Inflammation, Motor Neurons, Neural stem cells, Superoxide Dismutase, lcsh:Cytology, business.industry, Amyotrophic Lateral Sclerosis, BIO/13 - BIOLOGIA APPLICATA, Cell Differentiation, Immunosuppression, Cell Biology, medicine.disease, Neural stem cell, Rats, Transplantation, Disease Models, Animal, 030104 developmental biology, Spinal Cord, Disease Progression, Female, Microglia, Rats, Transgenic, Stem cell, business, 030217 neurology & neurosurgery
Abstract: Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.
Published: 2019
Full Text: View/download PDF

20. Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Author: Letizia Mazzini, Maurizio Gelati, Daniela Celeste Profico, Gianni Sorarù, Daniela Ferrari, Massimiliano Copetti, Gianmarco Muzi, Claudia Ricciolini, Sandro Carletti, Cesare Giorgi, Cristina Spera, Domenico Frondizi, Stefano Masiero, Alessandro Stecco, Carlo Cisari, Enrica Bersano, Fabiola De Marchi, Maria Francesca Sarnelli, Giorgia Querin, Roberto Cantello, Francesco Petruzzelli, Annamaria Maglione, Cristina Zalfa, Elena Binda, Alberto Visioli, Domenico Trombetta, Barbara Torres, Laura Bernardini, Alessandra Gaiani, Maurilio Massara, Silvia Paolucci, Nicholas M. Boulis, Angelo L. Vescovi, on behalf of the ALS‐NSCs Trial Study Group, Mazzini, L, Gelati, M, Profico, D, Soraru, G, Ferrari, D, Copetti, M, Muzi, G, Ricciolini, C, Carletti, S, Giorgi, C, Spera, C, Frondizi, D, Masiero, S, Stecco, A, Cisari, C, Bersano, E, Marchi, F, Sarnelli, M, Querin, G, Cantello, R, Petruzzelli, F, Maglione, A, Zalfa, C, Binda, E, Visioli, A, Trombetta, D, Torres, B, Bernardini, L, Gaiani, A, Massara, M, Paolucci, S, Boulis, N, and Vescovi, A
Subjects: Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Oncology, Pilot Projects, Fetal stem cells, Clinical trials, 0302 clinical medicine, Human Clinical Article, Neural Stem Cells, Adult stem cell, Amyotrophic lateral sclerosis, Injections, Spinal, Adult stem cells, lcsh:R5-920, lcsh:Cytology, Brain, General Medicine, Middle Aged, Magnetic Resonance Imaging, Neural stem cell, Clinical trial, Treatment Outcome, medicine.anatomical_structure, Spinal Cord, Female, Stem cell, lcsh:Medicine (General), Adult, medicine.medical_specialty, Cellular therapy, Pain, Young Adult, 03 medical and health sciences, Internal medicine, Glial Fibrillary Acidic Protein, medicine, Humans, lcsh:QH573-671, Adverse effect, Aged, business.industry, Brain-Derived Neurotrophic Factor, Amyotrophic Lateral Sclerosis, BIO/13 - BIOLOGIA APPLICATA, Cell Biology, medicine.disease, Spinal cord, Transplantation, 030104 developmental biology, Fetal stem cells, Amyotrophic Lateral Scleorsis, clinical trials, business, 030217 neurology & neurosurgery, Stem Cell Transplantation, Developmental Biology
Abstract: The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine 2019;8:887–897
Published: 2019

21. Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment

Author: Maurizio Gelati, Angelo L. Vescovi, Daniela Ferrari, Daniela Celeste Profico, Ferrari, D, Gelati, M, Profico, D, and Vescovi, A
Subjects: 0301 basic medicine, Fetal Tissue Transplantation, business.industry, Cell, mechanisms of cell differentiation, BIO/13 - BIOLOGIA APPLICATA, Cell Biology, Cell Maturation, Bioinformatics, Neural stem cell, Transplantation, Cell therapy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Cell culture, medicine, Brain Tissue Transplantation, business, 030217 neurology & neurosurgery, Developmental Biology, mechanisms of cell proliferation
Abstract: Clinical trials for Parkinson's disease, which used primary brain fetal tissue, have demonstrated that neural stem cell therapy could be suitable for neurodegenerative diseases. The use of fetal tissue presents several issues that have hampered the clinical development of this approach. In addition to the ethical concerns related to the required continuous supply of fetal specimen, the necessity to use cells from multiple fetuses in a single graft greatly compounded the problem. Cell viability and composition vary in different donors, and, further, the heterogeneity in the donor cells increased the probability of immunological rejection or contamination. An ideal cell source for cell therapy is one that is renewable, thus eliminating the need for transplantation of primary fetal tissue, and that also allows for viability, sterility, cell composition, and cell maturation to be controlled, while being inherently not tumorigenic. The availability of continuous and standardized clinical grade normal human neural cells, able to combine the plasticity of fetal tissue with an extensive proliferating capacity and functional stability, would be of paramount importance for the translation of cell therapy for central nervous system (CNS) disorders into the clinic. Here we describe a well-established protocol to produce human neural stem cells following GMP guidelines that allows us to obtain "clinical grade" cell lines.
Published: 2018

22. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?

Author: Miguel Blanquer, Enrica Bersano, Cesare Giorgi, Maurizio Gelati, Daniela Celeste Profico, Stephen B. Dunnett, Roberto Cantello, Nazem Atassi, Pierdavide Guenzi, Antonia Follenzi, Mariagrazia Grilli, Gabriele Panzarasa, Alessandro Vercelli, Letizia Mazzini, Fabiola De Marchi, Vincenzo Silani, M. Poloni, Pier Giorgio Car, Vincenzo La Bella, Caterina Bendotti, Angelo L. Vescovi, Ettore Beghi, Rossella Spataro, Roberto Fantozzi, Nicholas M. Boulis, Gianni Sorarù, Claudia Caponnetto, Adriano Chiò, Gianluigi Mancardi, Simona Brajkovic, Alessandro Stecco, Eva L. Feldman, Atassi, N, Beghi, E, Blanquer, M, Boulis, N, Cantello, R, Caponnetto, C, Chiò, A, Dunnett, S, Feldman, E, Vescovi, A, Mazzini, L, Bendotti, C, Bersano, E, Brajkovic, S, Car, P, De Marchi, F, Fantozzi, R, Follenzi, A, Gelati, M, Giorgi, C, Grilli, M, Guenzi, P, La Bella, V, Mancardi, G, Panzarasa, G, Poloni, M, Profico, D, Silani, V, Sorarù, G, Spataro, R, Stecco, A, and Vercelli, A
Subjects: 0301 basic medicine, Cancer Research, Cell- and Tissue-Based Therapy, 0302 clinical medicine, Public discussion, Neural Stem Cells, Immunology and Allergy, Neural Stem Cell, ALS, clinical trials, stem cells, transplantation, Immunology, Oncology, Genetics (clinical), Cell Biology, Transplantation, Amyotrophic lateral sclerosis, clinical trial, Middle Aged, Stem cell, Safety, Human, Adult, medicine.medical_specialty, Consensus, Adolescent, Consensu, 03 medical and health sciences, Therapeutic approach, Young Adult, Clinical Trials, Phase II as Topic, medicine, Humans, Intensive care medicine, Aged, business.industry, Amyotrophic Lateral Sclerosis, BIO/13 - BIOLOGIA APPLICATA, medicine.disease, stem cell, Clinical trial, 030104 developmental biology, Clinical Trials, Phase III as Topic, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi, Stem Cell Transplantation
Abstract: Intraspinal stem cell (SC) transplantation represents a new therapeutic approach for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable difficulties in designing future efficacy trials, some related to the field of ALS and some that are specific to SCs or the mode of delivery. In October 2015, the most controversial points on SC transplantation were addressed during an international workshop intended to bring together international SC and ALS researchers in a public discussion on a topic for which expertise is limited. During the meeting, a discussion was started on the basic structure of the ideal clinical trial testing the efficacy and safety of SC transplantation. The current document includes a number of consensus points reflecting the design of phase II/III clinical trials.
Published: 2016

23. Culturing and Expansion of 'Clinical Grade' Precursors Cells from the Fetal Human Central Nervous System

Author: Daniela Celeste Profico, Giada Sgaravizzi, Gianmarco Muzi, Angelo L. Vescovi, Maurizio Gelati, Massimo Projetti-Pensi, Reynolds, BA, Deleyrolle, LP, Gelati, M, Profico, D, Projetti Pensi, M, Muzi, G, Sgaravizzi, G, and Vescovi, A
Subjects: Cell physiology, Cell growth, Central nervous system, Biology, medicine.disease, Neural stem cell, Cell therapy, Clinical trial, medicine.anatomical_structure, Precursor cell, fetal human central nervous system, Immunology, medicine, Amyotrophic lateral sclerosis, Neuroscience
Abstract: NSCs have been demonstrated to be very useful in grafts into the mammalian central nervous system to investigate the exploitation of NSC for the therapy of neurodegenerative disorders in animal models of neurodegenerative diseases. To push cell therapy in CNS on stage of clinical application, it is necessary to establish a continuous and standardized, clinical grade (i.e., produced following the good manufacturing practice guidelines) human neural stem cell lines.In this chapter we will illustrate some of the protocols for the production and characterization routinely used into our GMP "cell factory" for the production of "clinical grade" human neural stem cell lines already in use in clinical trials on neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS- Clinicaltrials.gov number NCT01640067) and secondary progressive multiple sclerosis (SPMS- Clinicaltrials.gov number NCT03282760).
Published: 2013
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24. Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats.

Author: Zalfa C, Rota Nodari L, Vacchi E, Gelati M, Profico D, Boido M, Binda E, De Filippis L, Copetti M, Garlatti V, Daniele P, Rosati J, De Luca A, Pinos F, Cajola L, Visioli A, Mazzini L, Vercelli A, Svelto M, Vescovi AL, and Ferrari D
Subjects: Amyotrophic Lateral Sclerosis mortality, Amyotrophic Lateral Sclerosis therapy, Animals, Cell Differentiation, Cell Survival, Disease Models, Animal, Disease Progression, Female, Humans, Inflammation metabolism, Inflammation pathology, Kaplan-Meier Estimate, Male, Microglia cytology, Microglia metabolism, Motor Neurons metabolism, Neural Stem Cells cytology, Neural Stem Cells metabolism, Neurogenesis, Rats, Rats, Sprague-Dawley, Rats, Transgenic, Spinal Cord pathology, Superoxide Dismutase genetics, Amyotrophic Lateral Sclerosis pathology, Neural Stem Cells transplantation, Superoxide Dismutase metabolism
Abstract: Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3-L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3-L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.
Published: 2019
Full Text: View/download PDF

25. Culturing and expansion of "clinical grade" precursors cells from the fetal human central nervous system.

Author: Gelati M, Profico D, Projetti-Pensi M, Muzi G, Sgaravizzi G, and Vescovi AL
Subjects: Animals, Cell Proliferation, Central Nervous System cytology, Cryopreservation, Culture Media, Fetus cytology, Humans, Karyotyping, Mice, Mice, Nude, Neural Stem Cells transplantation, Spheroids, Cellular physiology, Stem Cell Niche, Tissue Banks, Neural Stem Cells physiology, Primary Cell Culture standards
Abstract: NSCs have been demonstrated to be very useful in grafts into the mammalian central nervous system to investigate the exploitation of NSC for the therapy of neurodegenerative disorders in animal models of neurodegenerative diseases. To push cell therapy in CNS on stage of clinical application, it is necessary to establish a continuous and standardized, clinical grade (i.e., produced following the good manufacturing practice guidelines) human neural stem cell lines. In this chapter, we illustrate some of the protocols routinely used into our GMP cell bank for the production of "clinical grade" human neural stem cell lines.
Published: 2013
Full Text: View/download PDF

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25 results on '"Profico, D"'

1. Human neural stem cells derived from fetal human brain communicate with each other and rescue ischemic neuronal cells through tunneling nanotubes

2. Preliminary data of intracerebroventricular transplantation of human-Neural Stem Cells in a mouse model of Amyotrophic Lateral Sclerosis

3. Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis

4. Culturing and Expansion of “Clinical Grade” Neural Stem Cells from the Fetal Human Central Nervous System

5. Human Neural Stem Cell-Based Drug Product: Clinical and Nonclinical Characterization

6. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

7. Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

8. Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats

9. Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

10. Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies

11. Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment

12. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

13. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?

14. N-3 fatty acids in patients with multiple cardiovascular risk factors

15. Human neural stem cell transplantation in ALS: Initial results from a phase I trial

16. Culturing and expansion of 'clinical grade' precursors cells from the fetal human central nervous system

17. Human Neural Stem Cell-Based Drug Product: Clinical and Nonclinical Characterization

18. Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

19. Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats

20. Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

21. Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment

22. Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?

23. Culturing and Expansion of 'Clinical Grade' Precursors Cells from the Fetal Human Central Nervous System

24. Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats.

25. Culturing and expansion of "clinical grade" precursors cells from the fetal human central nervous system.

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25 results on '"Profico, D"'

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