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3. Asparagine transport through SLC1A5/ASCT2 and SLC38A5/SNAT5 is essential for BCP‐ALL cell survival and a potential therapeutic target

Author

Taurino, Giuseppe, primary, Dander, Erica, additional, Chiu, Martina, additional, Pozzi, Giulia, additional, Maccari, Chiara, additional, Starace, Rita, additional, Silvestri, Daniela, additional, Griffini, Erika, additional, Bianchi, Massimiliano G., additional, Carubbi, Cecilia, additional, Andreoli, Roberta, additional, Mirandola, Prisco, additional, Valsecchi, Maria Grazia, additional, Rizzari, Carmelo, additional, D'Amico, Giovanna, additional, and Bussolati, Ovidio, additional

Published
2024
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4. ActivinA modulates B-Acute Lymphoblastic Leukaemia cell communication and survival by inducing extracellular vesicles production

Author

Licari, Eugenia, primary, Cricrì, Giulia, additional, Mauri, Mario, additional, Raimondo, Francesca, additional, Dioni, Laura, additional, Favero, Chiara, additional, Giussani, Alice, additional, Starace, Rita, additional, Nucera, Silvia, additional, Biondi, Andrea, additional, Piazza, Rocco, additional, Bollati, Valentina, additional, Dander, Erica, additional, and D'Amico, Giovanna, additional

Published
2024
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5. Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis

Author

Rambaldi, Benedetta, Diral, Elisa, Donsante, Samantha, Di Marzo, Noemi, Mottadelli, Federica, Cardinale, Lucia, Dander, Erica, Isimbaldi, Giuseppe, Pioltelli, Pietro, Biondi, Andrea, Riminucci, Mara, D’Amico, Giovanna, Elli, Elena Maria, Pievani, Alice, and Serafini, Marta

Published
2021
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9. The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease

Author

Dander, Erica, primary, Vinci, Paola, additional, Vetrano, Stefania, additional, Recordati, Camilla, additional, Piazza, Rocco, additional, Fazio, Grazia, additional, Bardelli, Donatella, additional, Bugatti, Mattia, additional, Sozio, Francesca, additional, Piontini, Andrea, additional, Bonanomi, Sonia, additional, Bertola, Luca, additional, Tassistro, Elena, additional, Valsecchi, Maria Grazia, additional, Calza, Stefano, additional, Vermi, William, additional, Biondi, Andrea, additional, Del Prete, Annalisa, additional, Sozzani, Silvano, additional, and D’Amico, Giovanna, additional

Published
2023
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11. The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease

Author

Dander, E, Vinci, P, Vetrano, S, Recordati, C, Piazza, R, Fazio, G, Bardelli, D, Bugatti, M, Sozio, F, Piontini, A, Bonanomi, S, Bertola, L, Tassistro, E, Valsecchi, M, Calza, S, Vermi, W, Biondi, A, Del Prete, A, Sozzani, S, D'Amico, G, Dander, Erica, Vinci, Paola, Vetrano, Stefania, Recordati, Camilla, Piazza, Rocco, Fazio, Grazia, Bardelli, Donatella, Bugatti, Mattia, Sozio, Francesca, Piontini, Andrea, Bonanomi, Sonia, Bertola, Luca, Tassistro, Elena, Valsecchi, Maria Grazia, Calza, Stefano, Vermi, William, Biondi, Andrea, Del Prete, Annalisa, Sozzani, Silvano, D'Amico, Giovanna, Dander, E, Vinci, P, Vetrano, S, Recordati, C, Piazza, R, Fazio, G, Bardelli, D, Bugatti, M, Sozio, F, Piontini, A, Bonanomi, S, Bertola, L, Tassistro, E, Valsecchi, M, Calza, S, Vermi, W, Biondi, A, Del Prete, A, Sozzani, S, D'Amico, G, Dander, Erica, Vinci, Paola, Vetrano, Stefania, Recordati, Camilla, Piazza, Rocco, Fazio, Grazia, Bardelli, Donatella, Bugatti, Mattia, Sozio, Francesca, Piontini, Andrea, Bonanomi, Sonia, Bertola, Luca, Tassistro, Elena, Valsecchi, Maria Grazia, Calza, Stefano, Vermi, William, Biondi, Andrea, Del Prete, Annalisa, Sozzani, Silvano, and D'Amico, Giovanna

Abstract

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1- KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD.

Published
2023

12. Study of Angiogenic Potential and Oxidative Metabolism in Mesenchymal Stromal Cells Derived from Shwachman-Diamond Syndrome Patients

Author

Gervasoni, Clarissa, primary, Giussani, Alice Martina, additional, Bertola, Nadia, additional, Dander, Erica, additional, Biondi, Andrea, additional, Corti, Paola, additional, Farruggia, Piero, additional, Menna, Giuseppe, additional, Cipolli, Marco, additional, Bezzerri, Valentino, additional, Pegoraro, Anna, additional, Cesaro, Simone, additional, Dufour, Carlo, additional, Cappelli, Enrico, additional, Ravera, Silvia, additional, and D'Amico, Giovanna, additional

Published
2022
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15. Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis

Author

Taurino, Giuseppe, primary, Deshmukh, Ruhi, additional, Villar, Victor H., additional, Chiu, Martina, additional, Shaw, Robin, additional, Hedley, Ann, additional, Shokry, Engy, additional, Sumpton, David, additional, Dander, Erica, additional, D'Amico, Giovanna, additional, Bussolati, Ovidio, additional, and Tardito, Saverio, additional

Published
2022
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16. Treatment of Graft versus Host Disease with Mesenchymal Stromal Cells: A Phase I Study on 40 Adult and Pediatric Patients

Author

Introna, Martino, Lucchini, Giovanna, Dander, Erica, Galimberti, Stefania, Rovelli, Attilio, Balduzzi, Adriana, Longoni, Daniela, Pavan, Fabio, Masciocchi, Francesca, Algarotti, Alessandra, Micò, Caterina, Grassi, Anna, Deola, Sara, Cavattoni, Irene, Gaipa, Giuseppe, Belotti, Daniela, Perseghin, Paolo, Parma, Matteo, Pogliani, Enrico, Golay, Josee, Pedrini, Olga, Capelli, Chiara, Cortelazzo, Sergio, D’Amico, Giovanna, Biondi, Andrea, Rambaldi, Alessandro, and Biagi, Ettore

Published
2014
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18. Platelet-lysate-Expanded Mesenchymal Stromal Cells as a Salvage Therapy for Severe Resistant Graft-versus-Host Disease in a Pediatric Population

Author

Lucchini, Giovanna, Introna, Martino, Dander, Erica, Rovelli, Attilio, Balduzzi, Adriana, Bonanomi, Sonia, Salvadè, Agnese, Capelli, Chiara, Belotti, Daniela, Gaipa, Giuseppe, Perseghin, Paolo, Vinci, Paola, Lanino, Edoardo, Chiusolo, Patrizia, Orofino, Maria Grazia, Marktel, Sarah, Golay, Jose, Rambaldi, Alessandro, Biondi, Andrea, D'Amico, Giovanna, and Biagi, Ettore

Published
2010
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19. ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment

Author

Chiu, M, Taurino, G, Dander, E, Bardelli, D, Fallati, A, Andreoli, R, Bianchi, M, Carubbi, C, Pozzi, G, Galuppo, L, Mirandola, P, Rizzari, C, Tardito, S, Biondi, A, D'Amico, G, Bussolati, O, Chiu, Martina, Taurino, Giuseppe, Dander, Erica, Bardelli, Donatella, Fallati, Alessandra, Andreoli, Roberta, Bianchi, Massimiliano G, Carubbi, Cecilia, Pozzi, Giulia, Galuppo, Laura, Mirandola, Prisco, Rizzari, Carmelo, Tardito, Saverio, Biondi, Andrea, D'Amico, Giovanna, Bussolati, Ovidio, Chiu, M, Taurino, G, Dander, E, Bardelli, D, Fallati, A, Andreoli, R, Bianchi, M, Carubbi, C, Pozzi, G, Galuppo, L, Mirandola, P, Rizzari, C, Tardito, S, Biondi, A, D'Amico, G, Bussolati, O, Chiu, Martina, Taurino, Giuseppe, Dander, Erica, Bardelli, Donatella, Fallati, Alessandra, Andreoli, Roberta, Bianchi, Massimiliano G, Carubbi, Cecilia, Pozzi, Giulia, Galuppo, Laura, Mirandola, Prisco, Rizzari, Carmelo, Tardito, Saverio, Biondi, Andrea, D'Amico, Giovanna, and Bussolati, Ovidio

Abstract

Mechanisms underlying the resistance of acute lymphoblastic leukemia (ALL) blasts to L-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to L-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid tradeoff. ALL blasts synthesize and secrete glutamine, thus increasing extracellular glutamine availability for stromal cells. In turn, MSCs use glutamine, either synthesized through glutamine synthetase (GS) or imported, to produce asparagine, which is then extruded to sustain asparagine-auxotroph leukemic cells. GS inhibition prevents mesenchymal cells adaptation to t-asparaginase, lowers glutamine secretion by ALL blasts, and markedly hinders the protection exerted by MSCs on leukemic cells. The pro-survival amino acid exchange is hindered by the inhibition or silencing of the asparagine efflux transporter SNAT5, which is induced in mesenchymal cells by ALL blasts. Consistently, primary MSCs from ALL patients express higher levels of SNAT5 (P < .05), secrete more asparagine (P < .05), and protect leukemic blasts (P < .05) better than MSCs isolated from healthy donors. In conclusion, ALL blasts arrange a pro-leukemic amino acid trade-off with bone marrow mesenchymal cells, which depends on GS and SNAT5 and promotes leukemic cell survival during L-asparaginase treatment.

Published
2021

23. Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B‐cell acute lymphoblastic leukaemia

Author

Dander, Erica, primary, Fallati, Alessandra, additional, Gulić, Tamara, additional, Pagni, Fabio, additional, Gaspari, Stefania, additional, Silvestri, Daniela, additional, Cricrì, Giulia, additional, Bedini, Gloria, additional, Portale, Federica, additional, Buracchi, Chiara, additional, Starace, Rita, additional, Pasqualini, Fabio, additional, D'Angiò, Mariella, additional, Brizzolara, Lisa, additional, Maglia, Oscar, additional, Mantovani, Alberto, additional, Garlanda, Cecilia, additional, Valsecchi, Maria Grazia, additional, Locatelli, Franco, additional, Biondi, Andrea, additional, Bottazzi, Barbara, additional, Allavena, Paola, additional, and D'Amico, Giovanna, additional

Published
2021
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25. Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability

Author

Chiu, Martina, primary, Toscani, Denise, additional, Marchica, Valentina, additional, Taurino, Giuseppe, additional, Costa, Federica, additional, Bianchi, Massimiliano G., additional, Andreoli, Roberta, additional, Franceschi, Valentina, additional, Storti, Paola, additional, Burroughs-Garcia, Jessica, additional, Eufemiese, Rosa Alba, additional, Dalla Palma, Benedetta, additional, Campanini, Nicoletta, additional, Martella, Eugenia, additional, Mancini, Cristina, additional, Shan, Jixiu, additional, Kilberg, Michael S., additional, D’Amico, Giovanna, additional, Dander, Erica, additional, Agnelli, Luca, additional, Pruneri, Giancarlo, additional, Donofrio, Gaetano, additional, Bussolati, Ovidio, additional, and Giuliani, Nicola, additional

Published
2020
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26. Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis

Author

Rambaldi, Benedetta, primary, Diral, Elisa, additional, Donsante, Samantha, additional, Di Marzo, Noemi, additional, Mottadelli, Federica, additional, Cardinale, Lucia, additional, Dander, Erica, additional, Isimbaldi, Giuseppe, additional, Pioltelli, Pietro, additional, Biondi, Andrea, additional, Riminucci, Mara, additional, D’Amico, Giovanna, additional, Elli, Elena Maria, additional, Pievani, Alice, additional, and Serafini, Marta, additional

Published
2020
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27. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer's disease

Author

Losurdo, Morris, primary, Pedrazzoli, Matteo, additional, D'Agostino, Claudia, additional, Elia, Chiara A., additional, Massenzio, Francesca, additional, Lonati, Elena, additional, Mauri, Mario, additional, Rizzi, Laura, additional, Molteni, Laura, additional, Bresciani, Elena, additional, Dander, Erica, additional, D'Amico, Giovanna, additional, Bulbarelli, Alessandra, additional, Torsello, Antonio, additional, Matteoli, Michela, additional, Buffelli, Mario, additional, and Coco, Silvia, additional

Published
2020
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29. Pro‐inflammatory cytokines favor the emergence of ETV6‐RUNX1‐positive pre‐leukemic cells in a model of mesenchymal niche

Author

Beneforti, Linda, primary, Dander, Erica, additional, Bresolin, Silvia, additional, Bueno, Clara, additional, Acunzo, Denise, additional, Bertagna, Mayla, additional, Ford, Anthony, additional, Gentner, Bernhard, additional, Kronnie, Geertruy te, additional, Vergani, Patrizia, additional, Menéndez, Pablo, additional, Biondi, Andrea, additional, D’Amico, Giovanna, additional, Palmi, Chiara, additional, and Cazzaniga, Giovanni, additional

Published
2020
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31. Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex

Author

Macagno, Annalisa, Bernasconi, Nadia L., Vanzetta, Fabrizia, Dander, Erica, Sarasini, Antonella, Revello, Maria Grazia, Gerna, Giuseppe, Sallusto, Federica, Lanzavecchia, Antonio, Macagno, Annalisa, Bernasconi, Nadia L., Vanzetta, Fabrizia, Dander, Erica, Sarasini, Antonella, Revello, Maria Grazia, Gerna, Giuseppe, Sallusto, Federica, and Lanzavecchia, Antonio

Abstract

Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immunocompromised patients and infected fetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (90% inhibitory concentration [IC90] values ranging from 5 to 200 pM) HCMV infection of endothelial, epithelial, and myeloid cells. With the single exception of an antibody that bound to a conserved epitope in the UL128 gene product, all other antibodies bound to conformational epitopes that required expression of two or more proteins of the gH/gL/UL128-131A complex. Antibodies against gB, gH, or gM/gN were also isolated and, albeit less potent, were able to neutralize infection of both endothelial-epithelial cells and fibroblasts. This study describes unusually potent neutralizing antibodies against HCMV that might be used for passive immunotherapy and identifies, through the use of such antibodies, novel antigenic targets in HCMV for the design of immunogens capable of eliciting previously unknown neutralizing antibody responses.

Published
2019

32. Mesenchymal stromal cells from Shwachman-Diamond syndrome patients fail to recreate a bone marrow niche in vivo and exhibit impaired angiogenesis

Author

Bardelli, D, Dander, E, Bugarin, C, Cappuzzello, C, Pievani, A, Fazio, G, Pierani, P, Corti, P, Farruggia, P, Dufour, C, Cesaro, S, Cipolli, M, Biondi, A, D'Amico, G, Bardelli, Donatella, Dander, Erica, Bugarin, Cristina, Cappuzzello, Claudia, Pievani, Alice, Fazio, Grazia, Pierani, Paolo, Corti, Paola, Farruggia, Piero, Dufour, Carlo, Cesaro, Simone, Cipolli, Marco, Biondi, Andrea, D'Amico, Giovanna, Bardelli, D, Dander, E, Bugarin, C, Cappuzzello, C, Pievani, A, Fazio, G, Pierani, P, Corti, P, Farruggia, P, Dufour, C, Cesaro, S, Cipolli, M, Biondi, A, D'Amico, G, Bardelli, Donatella, Dander, Erica, Bugarin, Cristina, Cappuzzello, Claudia, Pievani, Alice, Fazio, Grazia, Pierani, Paolo, Corti, Paola, Farruggia, Piero, Dufour, Carlo, Cesaro, Simone, Cipolli, Marco, Biondi, Andrea, and D'Amico, Giovanna

Abstract

Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model. We show that the ability of semi-cartilaginous pellets (SCPs) derived from SDS-MSCs to generate complete heterotopic ossicles in vivo is severely impaired in comparison with HD-MSC-derived SCPs. Specifically, after in vitro angiogenic stimuli, SDS-MSCs showed a defective ability to form correct networks, capillary tubes and vessels and displayed a marked decrease in VEGFA expression. Altogether, these findings unveil a novel mechanism of SDS-mediated haematopoietic dysfunction based on hampered ability of SDS-MSCs to support angiogenesis. Overall, MSCs could represent a new appealing therapeutic target to treat dysfunctional haematopoiesis in paediatric SDS patients

Published
2018

33. Additional file 1: of Intraperitoneal adoptive transfer of mesenchymal stem cells enhances recovery from acid aspiration acute lung injury in mice

Author

Mauri, Tommaso, Zambelli, Vanessa, Cappuzzello, Claudia, Bellani, Giacomo, Dander, Erica, Sironi, Marina, Castiglioni, Vittoria, Doni, Andrea, Mantovani, Alberto, Biondi, Andrea, Garlanda, Cecilia, D’Amico, Giovanna, and Pesenti, Antonio

Abstract

Detailed methods and additional results. (DOCX 838 kb)

Published
2017
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34. Bone Marrow Mesenchymal Stromal Cells and Inflammation Contribute to ETV6-RUNX1+ Preleukemic Cells Persistence and DNA Damaging

Author

Beneforti, Linda, primary, Dander, Erica, additional, Bresolin, Silvia, additional, Bueno, Clara, additional, te Kronnie, Geertruy, additional, Ford, Anthony, additional, Menendez, Pablo, additional, D'Amico, Giovanna, additional, Biondi, Andrea, additional, Palmi, Chiara, additional, and Cazzaniga, Giovanni, additional

Published
2018
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35. Activin A, a Potential Key Factor of the Malignant Bone Marrow Niche, Enhances B-Cell Precursor-Acute Lymphoblastic Leukemic Cell Migratory and Invasive Properties

Author

Dander, Erica, primary, Portale, Federica, additional, Silvestri, Daniela, additional, Cricrì, Giulia, additional, Bresolin, Silvia, additional, Gaspari, Stefania, additional, Russo, Barbara, additional, Lupi, Monica, additional, Ubezio, Paolo, additional, te Kronnie, Geertruy, additional, Valsecchi, Maria Grazia, additional, Locatelli, Franco, additional, Rizzari, Carmelo, additional, Biondi, Andrea, additional, and D'Amico, Giovanna, additional

Published
2018
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36. ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells

Author

Portale, Federica, primary, Cricrì, Giulia, additional, Bresolin, Silvia, additional, Lupi, Monica, additional, Gaspari, Stefania, additional, Silvestri, Daniela, additional, Russo, Barbara, additional, Marino, Noemi, additional, Ubezio, Paolo, additional, Pagni, Fabio, additional, Vergani, Patrizia, additional, Kronnie, Geertruy Te, additional, Valsecchi, Maria Grazia, additional, Locatelli, Franco, additional, Rizzari, Carmelo, additional, Biondi, Andrea, additional, Dander, Erica, additional, and D’Amico, Giovanna, additional

Published
2018
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37. Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

Author

Scutera, Sara, primary, Salvi, Valentina, additional, Lorenzi, Luisa, additional, Piersigilli, Giorgia, additional, Lonardi, Silvia, additional, Alotto, Daniela, additional, Casarin, Stefania, additional, Castagnoli, Carlotta, additional, Dander, Erica, additional, D’Amico, Giovanna, additional, Sozzani, Silvano, additional, and Musso, Tiziana, additional

Published
2018
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38. Mesenchymal stromal cells from Shwachman-Diamond syndrome patients fail to recreate a bone marrow nichein vivoand exhibit impaired angiogenesis

Author

Bardelli, Donatella, primary, Dander, Erica, additional, Bugarin, Cristina, additional, Cappuzzello, Claudia, additional, Pievani, Alice, additional, Fazio, Grazia, additional, Pierani, Paolo, additional, Corti, Paola, additional, Farruggia, Piero, additional, Dufour, Carlo, additional, Cesaro, Simone, additional, Cipolli, Marco, additional, Biondi, Andrea, additional, and D'Amico, Giovanna, additional

Published
2018
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39. Intraperitoneal adoptive transfer of mesenchymal stem cells enhances recovery from acid aspiration acute lung injury in mice

Author

Mauri, T, Zambelli, V, Cappuzzello, C, Bellani, G, Dander, E, Sironi, M, Castiglioni, V, Doni, A, Mantovani, A, Biondi, A, Garlanda, C, D'Amico, G, Pesenti, A, MAURI, TOMMASO, ZAMBELLI, VANESSA, CAPPUZZELLO, CLAUDIA, BELLANI, GIACOMO, DANDER, ERICA, BIONDI, ANDREA, PESENTI, ANTONIO MARIA, Mauri, T, Zambelli, V, Cappuzzello, C, Bellani, G, Dander, E, Sironi, M, Castiglioni, V, Doni, A, Mantovani, A, Biondi, A, Garlanda, C, D'Amico, G, Pesenti, A, MAURI, TOMMASO, ZAMBELLI, VANESSA, CAPPUZZELLO, CLAUDIA, BELLANI, GIACOMO, DANDER, ERICA, BIONDI, ANDREA, and PESENTI, ANTONIO MARIA

Abstract

Mesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3.

Published
2017

40. Mesenchymal stromal cell-secreted chemerin is a novel immunomodulatory molecule driving the migration of ChemR23-expressing cells

Author

Vinci, P, Bastone, A, Schiarea, S, Cappuzzello, C, Del Prete, A, Dander, E, Biondi, A, D'Amico, G, VINCI, PAOLA, CAPPUZZELLO, CLAUDIA, DANDER, ERICA, BIONDI, ANDREA, D'Amico, G., Vinci, P, Bastone, A, Schiarea, S, Cappuzzello, C, Del Prete, A, Dander, E, Biondi, A, D'Amico, G, VINCI, PAOLA, CAPPUZZELLO, CLAUDIA, DANDER, ERICA, BIONDI, ANDREA, and D'Amico, G.

Abstract

Background Mesenchymal stromal cells (MSCs) are multipotent cells characterized by broad immunomodulatory properties exploited for the treatment of inflammatory disorders. However, the efficacy of MSC-based therapy is highly variable and tightly linked to MSC culture conditions and treatment schedule. Thus, the identification of novel key molecules regulating MSC immunomodulatory activities in vivo might constitute a crucial step toward the optimization of currently available clinical protocols. In this regard, herein, we sought to determine whether the newly identified chemotactic protein, chemerin, plays a role in MSC-mediated regulation of inflammation. Methods Chemerin production by human MSCs was investigated under different culture conditions using enzyme-linked immunosorbent assay (ELISA). After purification, MSC-secreted chemerin was identified using mass spectrometry analysis and the biological activity of secreted isoforms was evaluated using migration assay. Results Bone marrow–derived MSCs secrete chemerin and express its receptors ChemR23 and CCRL2. Chemerin production is dependent on culture conditions and increases upon stimulation with inflammatory cytokines. In particular, platelet lysate (PL)-MSCs produce higher levels of chemerin compared with fetal bovine serum (FBS)-MSCs. Furthermore, chemerin is secreted by MSCs as an inactive precursor, which can be converted into its active form by exogenous chemerin-activating serine and cysteine proteases. Discussion Our data indicate that, in response to various inflammatory stimuli, MSCs secrete high amounts of inactive chemerin, which can then be activated by inflammation-induced tissue proteases. In light of these initial findings, we propose that further analysis of chemerin functions in vivo might constitute a crucial step toward optimizing MSC-based therapy for inflammatory diseases.

Published
2017

41. Autophagy and Glutamine Synthetase Induction Sustain ALL Blast Resistance to L‐Asparaginase in Human Bone Marrow Mesenchymal Stromal Cells

Author

Chiu, Martina, primary, Bardelli, Donatella, additional, Taurino, Giuseppe, additional, Dander, Erica, additional, Bianchi, Massimiliano G, additional, Mirandola, Prisco, additional, Carubbi, Cecilia, additional, D'Amico, Giovanna, additional, Rizzari, Carmelo, additional, and Bussolati, Ovidio, additional

Published
2017
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42. Intranasal delivery of mesenchymal stem cell‐derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTgmodel of Alzheimer's disease

Author

Losurdo, Morris, Pedrazzoli, Matteo, D'Agostino, Claudia, Elia, Chiara A., Massenzio, Francesca, Lonati, Elena, Mauri, Mario, Rizzi, Laura, Molteni, Laura, Bresciani, Elena, Dander, Erica, D'Amico, Giovanna, Bulbarelli, Alessandra, Torsello, Antonio, Matteoli, Michela, Buffelli, Mario, and Coco, Silvia

Abstract

The critical role of neuroinflammation in favoring and accelerating the pathogenic process in Alzheimer's disease (AD) increased the need to target the cerebral innate immune cells as a potential therapeutic strategy to slow down the disease progression. In this scenario, mesenchymal stem cells (MSCs) have risen considerable interest thanks to their immunomodulatory properties, which have been largely ascribed to the release of extracellular vesicles (EVs), namely exosomes and microvesicles. Indeed, the beneficial effects of MSC‐EVs in regulating the inflammatory response have been reported in different AD mouse models, upon chronic intravenous or intracerebroventricular administration. In this study, we use the triple‐transgenic 3xTg mice showing for the first time that the intranasal route of administration of EVs, derived from cytokine‐preconditioned MSCs, was able to induce immunomodulatory and neuroprotective effects in AD. MSC‐EVs reached the brain, where they dampened the activation of microglia cells and increased dendritic spine density. MSC‐EVs polarized in vitro murine primary microglia toward an anti‐inflammatory phenotype suggesting that the neuroprotective effects observed in transgenic mice could result from a positive modulation of the inflammatory status. The possibility to administer MSC‐EVs through a noninvasive route and the demonstration of their anti‐inflammatory efficacy might accelerate the chance of a translational exploitation of MSC‐EVs in AD. In a preclinical model of Alzheimer's disease, characterized by neuronal damage and a high rate of inflammation (left), the intranasal (IN) administration of extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) operates in dampening inflammation (by reducing microglia activation) and in inducing neuroprotective effects (by decreasing spine loss) (right). These data suggest the possibility that the IN route administration of MSC‐EVs might accelerate the chance of a translational exploitation of MSC‐EVs toward therapy.

Published
2020
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43. Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

Author

Dander, E, Lorenzo, P, Bottazzi, B, Quarello, P, Vinci, P, Balduzzi, A, Masciocchi, F, Bonanomi, S, Cappuzzello, C, Prunotto, G, Pavan, F, Pasqualini, F, Sironi, M, Cuccovillo, I, Leone, R, Salvatori, G, Parma, M, Terruzzi, E, Pagni, F, Locatelli, F, Mantovani, A, Fagioli, F, Biondi, A, Garlanda, C, Valsecchi, M, Rovelli, A, D'Amico, G, DANDER, ERICA, VINCI, PAOLA, MASCIOCCHI, FRANCESCA, BONANOMI, SONIA, CAPPUZZELLO, CLAUDIA, PRUNOTTO, GIULIA, PAVAN, FABIO, PAGNI, FABIO, BIONDI, ANDREA, VALSECCHI, MARIA GRAZIA, D'Amico, G., Dander, E, Lorenzo, P, Bottazzi, B, Quarello, P, Vinci, P, Balduzzi, A, Masciocchi, F, Bonanomi, S, Cappuzzello, C, Prunotto, G, Pavan, F, Pasqualini, F, Sironi, M, Cuccovillo, I, Leone, R, Salvatori, G, Parma, M, Terruzzi, E, Pagni, F, Locatelli, F, Mantovani, A, Fagioli, F, Biondi, A, Garlanda, C, Valsecchi, M, Rovelli, A, D'Amico, G, DANDER, ERICA, VINCI, PAOLA, MASCIOCCHI, FRANCESCA, BONANOMI, SONIA, CAPPUZZELLO, CLAUDIA, PRUNOTTO, GIULIA, PAVAN, FABIO, PAGNI, FABIO, BIONDI, ANDREA, VALSECCHI, MARIA GRAZIA, and D'Amico, G.

Abstract

Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acutephase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of transplantation, likely due to conditioning, and at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was also found increased in skin and colon biopsies from patients with active disease. Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome since they resulted significantly higher in both severe and therapyunresponsive patients. Multiple injections of rhPTX3 in the murine model of GvHD did not influence the disease course. Taken together, our results indicate that PTX3 constitutes a biomarker of GvHD severity and therapy response useful to tailor treatment intensity according to early risk-stratification of GvHD patients.

Published
2016

44. Mesenchymal stromal cell-derived PTX3 promotes wound healing via fibrin remodeling

Author

Cappuzzello, C, Doni, A, Dander, E, Pasqualini, F, Nebuloni, M, Bottazzi, B, Mantovani, A, Biondi, A, Garlanda, C, D'Amico, G, CAPPUZZELLO, CLAUDIA, DANDER, ERICA, BIONDI, ANDREA, D'Amico, G., Cappuzzello, C, Doni, A, Dander, E, Pasqualini, F, Nebuloni, M, Bottazzi, B, Mantovani, A, Biondi, A, Garlanda, C, D'Amico, G, CAPPUZZELLO, CLAUDIA, DANDER, ERICA, BIONDI, ANDREA, and D'Amico, G.

Abstract

Although mesenchymal stromal cells (MSCs) can promote wound healing in different clinical settings, the underlying mechanism of MSC-mediated tissue repair has yet to be determined. Because a nonredundant role of pentraxin 3 (PTX3) in tissue repair and remodeling has been recently described, here we sought to determine whether MSC-derived PTX3 might play a role in wound healing. Using a murine model of skin repair, we found that Ptx3-deficient (Ptx3-/-) MSCs delayed wound closure and reduced granulation tissue formation compared with wt MSCs. At day 2, confocal microscopy revealed a dramatic reduction in green fluorescent protein (GFP)-expressing Ptx3-/-MSCs recruited to the wound, where they appeared to be not only poorly organized in bundles but also scattered in the extracellular matrix. These findings were further confirmed by quantitative biochemical analysis of GFP content in wound extracts. Furthermore, Ptx3-/-MSC-treated skins displayed increased levels of fibrin and lower levels of D-dimer, suggesting delayed fibrin-rich matrix remodeling compared with control skins. Consistently, both pericellular fibrinolysis and migration through fibrin were found to be severely affected in Ptx3-/-MSCs. Overall, our findings identify an essential role of MSC-derived PTX3 in wound repair underscoring the beneficial potential of MSC-based therapy in the management of intractable wounds.

Published
2016

45. Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

Author

Dander, Erica, primary, De Lorenzo, Paola, additional, Bottazzi, Barbara, additional, Quarello, Paola, additional, Vinci, Paola, additional, Balduzzi, Adriana, additional, Masciocchi, Francesca, additional, Bonanomi, Sonia, additional, Cappuzzello, Claudia, additional, Prunotto, Giulia, additional, Pavan, Fabio, additional, Pasqualini, Fabio, additional, Sironi, Marina, additional, Cuccovillo, Ivan, additional, Leone, Roberto, additional, Salvatori, Giovanni, additional, Parma, Matteo, additional, Terruzzi, Elisabetta, additional, Pagni, Fabio, additional, Locatelli, Franco, additional, Mantovani, Alberto, additional, Fagioli, Franca, additional, Biondi, Andrea, additional, Garlanda, Cecilia, additional, Valsecchi, Maria Grazia, additional, Rovelli, Attilio, additional, and D'Amico, Giovanna, additional

Published
2016
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