74 results on '"Miceli, V."'
Search Results
2. Mesenchymal Stem/Stromal Cells: HIGH-RESOLUTION MASS-SPECTROMETRY-BASED PROTEOMICS AND FUNCTIONAL VALIDATION REVEALED DISTINCT THERAPEUTIC CAPABILITIES RELATED TO DIFFERENT PRIMING STRATEGIES IN MESENCHYMAL STROMAL/STEM CELLS: POTENTIAL IMPLICATIONS FOR THEIR CLINICAL USE
- Author
-
Miceli, V., primary, Scilabra, S.D., additional, Calligaris, M., additional, Zito, G., additional, Busà, R., additional, Gallo, A., additional, Bulati, M., additional, and Conaldi, P., additional
- Published
- 2023
- Full Text
- View/download PDF
3. I progetti ENEA per l'economia circolare
- Author
-
Caretto, F., Antonini, M., Protopapa, M. L., Tammaro, M., Fontana, Danilo, Mingazzini, C., Tuffi, R., Chiavetta, C., Vellucci, F., Nanni, V., Di Bari, C., Ceruti, F., Forte, F., Luciano, A., Miceli, V., Molino, A., Sbaffoni, S., Zoani, C., Cafiero, L. M., Zucaro, A., Petta, L., Ferraris, M., Giuliano, Antonio, Spagni, A., Barberio, G., Cutaia, L., Brunori, C., Castelli, S., Innella, C., Rinaldi, C., Caretto, F., Antonini, M., Protopapa, M. L., Tammaro, M., Fontana, Danilo, Mingazzini, C., Tuffi, R., Chiavetta, C., Vellucci, F., Nanni, V., Di Bari, C., Ceruti, F., Forte, F., Luciano, A., Miceli, V., Molino, A., Sbaffoni, S., Zoani, C., Cafiero, L. M., Zucaro, A., Petta, L., Ferraris, M., Giuliano, Antonio, Spagni, A., Barberio, G., Cutaia, L., Brunori, C., Castelli, S., Innella, C., and Rinaldi, C.
- Subjects
Biotecnologie e agroindustria ,Strumenti per la transizione circolare ,Materie prime e prodotti ,Territorio e città - Abstract
Nell’ambito della sua mission di Agenzia Nazionale per le nuove tecnologie, l’energia e lo sviluppo economico sostenibile, l’ENEA è focalizzata in modo preminente sulla ricerca ‘applicata’, ovvero sul rendere disponibili tecnologie innovative e servizi avanzati nei diversi settori di competenza, al mondo delle imprese, alle pubbliche amministrazioni e agli stessi cittadini . Da questo punto di vista, l’economia circolare è una delle priorità strategiche e si concretizza attraverso numerosi progetti operativi con l’obiettivo di andare ‘oltre gli slogan’ e tradurre in realtà il principio fondante della chiusura dei cicli, quale volano di crescita e competitività e, allo stesso tempo, strumento essenziale per un modello di società incentrato sulla sostenibilità. In questo opuscolo sono illustrati alcuni dei progetti, delle iniziative e delle attività, ma anche gli strumenti, le metodologie, gli approcci e i modelli che ENEA sta mettendo in campo per supportare la trasformazione verso l’economia circolare, con un focus anche sulla formazione ed informazione, aspetti di grande rilievo per operare il cambiamento culturale e di comportamenti necessario. In questi progetti il Dipartimento “Sostenibilità dei Sistemi Produttivi e Territoriali” (SSPT) ha un ruolo di primo piano, come coordinatore o referente di attività in collaborazione con altri Dipartimenti dell’Agenzia, partner nazionali ed internazionali, imprese e istituzioni centrali locali, ed altri soggetti a livello territoriale e urbano. Queste attività impegnano oltre cento ricercatori e tecnologi del Dipartimento SSPT e una rete di infrastrutture, hall tecnologiche, impianti pilota e laboratori analitici avanzati specializzati nell’eco-innovazione di processo, di prodotto e di sistema. I progetti consentono di applicare l’economia circolare in diversi ambiti applicativi quali: • Aree urbane: ENEA progetta e sviluppa modelli e sistemi di gestione integrata e circolare di funzionamento urbano per città più sostenibili, circolari e inclusive, per promuovere stili di vita e consumo sostenibili, per effettuare una corretta gestione dell’acqua e dei rifiuti urbani anche in chiave di valorizzazione, salvaguardare salute e sicurezza, stimolare le industrie culturali, turismo e best practices in contesti urbani e periurbani; • Territorio e mare: ENEA pianifica e sviluppa processi e metodologie per la gestione sostenibile di territorio e mare in ottica di economia circolare attraverso la Gestione porti e aree costiere, il Turismo sostenibile, lo sviluppo della filiera ittica; • Sistema industriale: ENEA sviluppa e implementa tecnologie e metodologie per modelli di produzione e consumo più sostenibili e rigenerativi a supporto dell’industria con tecnologie innovative e nuovi modelli di business (simbiosi industriale, Modelli di circular design, Sharing economy, etc), strumenti per le imprese, riqualificazione di siti industriali in ottica circolare; • Catena del valore: ENEA sviluppa approcci di sistema per promuovere e facilitare la chiusura dei cicli nelle filiere produttive e lungo il ciclo di vita di prodotti e materiali attraverso attività per promuovere la collaborazione tra diversi attori e settori, approccio integrato e multidisciplinare (life cycle thinking e misura della circolarità), nuovi modelli di business e analisi di mercato.
- Published
- 2023
4. Post treatment imaging in patients with local advanced cervical carcinoma
- Author
-
Ciulla, S., primary, Celli, V., additional, Aiello, A. A., additional, Gigli, S., additional, Ninkova, R., additional, Miceli, V., additional, Ercolani, G., additional, Dolciami, M., additional, Ricci, P., additional, Palaia, I., additional, Catalano, C., additional, and Manganaro, L., additional
- Published
- 2022
- Full Text
- View/download PDF
5. Role of non-coding RNAs in age-related vascular cognitive impairment: An overview on diagnostic/prognostic value in Vascular Dementia and Vascular Parkinsonism
- Author
-
Miceli, V., primary, Russelli, G., additional, Iannolo, G., additional, Gallo, A., additional, Lo Re, V., additional, Agnese, V., additional, Sparacia, G., additional, Conaldi, P.G., additional, and Bulati, M., additional
- Published
- 2020
- Full Text
- View/download PDF
6. Placenta-derived mesenchymal stem cells enhance human liver organoid maturation: translational implications for liver regeneration
- Author
-
Miceli, V., primary, Nigro, A. Lo, additional, Pampalone, M., additional, Vitale, G., additional, and Conaldi, P., additional
- Published
- 2020
- Full Text
- View/download PDF
7. 176 - Mesenchymal Stem/Stromal Cells: HIGH-RESOLUTION MASS-SPECTROMETRY-BASED PROTEOMICS AND FUNCTIONAL VALIDATION REVEALED DISTINCT THERAPEUTIC CAPABILITIES RELATED TO DIFFERENT PRIMING STRATEGIES IN MESENCHYMAL STROMAL/STEM CELLS: POTENTIAL IMPLICATIONS FOR THEIR CLINICAL USE
- Author
-
Miceli, V., Scilabra, S.D., Calligaris, M., Zito, G., Busà, R., Gallo, A., Bulati, M., and Conaldi, P.
- Subjects
- *
STROMAL cells , *STEM cells , *MESENCHYMAL stem cells - Published
- 2023
- Full Text
- View/download PDF
8. Protective effect of carnosine on oxidative stress injury in pancreatic β–cells
- Author
-
Miceli, V, Frazziano, G, Grasso, Giuseppe, Rizzarelli, E, Iannolo, G, and Conaldi, Pg
- Published
- 2015
9. Disciplina di rigore fiscale e sistemi federalistici
- Author
-
Bassanini F., Cerniglia F., Quadrio Curzio A., Caldirola D., Miceli V., Bassanini F, Cerniglia F., Boschetti, Barbara, Boschetti, Barbara (ORCID:0000-0001-9344-2163), Bassanini F., Cerniglia F., Quadrio Curzio A., Caldirola D., Miceli V., Bassanini F, Cerniglia F., Boschetti, Barbara, and Boschetti, Barbara (ORCID:0000-0001-9344-2163)
- Abstract
L'articolo analizza, in chiave comparata, l'impatto delle norme di rigore fiscale sui sistemi autonomistici
- Published
- 2016
10. In vitro imaging of β-cells using fluorescent cubic bicontinuous liquid crystalline nanoparticles
- Author
-
Miceli, V., primary, Meli, V., additional, Blanchard-Desce, M., additional, Bsaibess, T., additional, Pampalone, M., additional, Conaldi, P. G., additional, Caltagirone, C., additional, Obiols-Rabasa, M., additional, Schmidt, J., additional, Talmon, Y., additional, Casu, A., additional, and Murgia, S., additional
- Published
- 2016
- Full Text
- View/download PDF
11. Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications
- Author
-
Giusi Alberti, Eleonora Russo, Simona Corrao, Rita Anzalone, Peter Kruzliak, Vitale Miceli, Pier Giulio Conaldi, Francesca Di Gaudio, Giampiero La Rocca, Alberti G., Russo E., Corrao S., Anzalone R., Kruzliak P., Miceli V., Conaldi P.G., Di Gaudio F., and La Rocca G.
- Subjects
Settore BIO/17 - Istologia ,adult mesenchymal stromal cells ,bone marrow ,inflammation ,regeneration ,cell-free therapies ,cancer ,Medicine (miscellaneous) ,tissue repair ,extracellular vesicles ,General Biochemistry, Genetics and Molecular Biology ,adipose tissue - Abstract
Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of parental cells were maintained by isolated EV populations. This review analyzes the recent development in the field of cell-free therapies, focusing on several adult tissues as a source of MSC-derived EVs and the available clinical data from in vivo models.
- Published
- 2022
12. Changes in the Transcriptome Profiles of Human Amnion-Derived Mesenchymal Stromal/Stem Cells Induced by Three-Dimensional Culture: A Potential Priming Strategy to Improve Their Properties
- Author
-
Alessia Gallo, Nicola Cuscino, Flavia Contino, Matteo Bulati, Mariangela Pampalone, Giandomenico Amico, Giovanni Zito, Claudia Carcione, Claudio Centi, Alessandro Bertani, Pier Giulio Conaldi, Vitale Miceli, Gallo A., Cuscino N., Contino F., Bulati M., Pampalone M., Amico G., Zito G., Carcione C., Centi C., Bertani A., Conaldi P.G., and Miceli V.
- Subjects
QH301-705.5 ,Cell Culture Techniques ,Cell Separation ,Regenerative Medicine ,Article ,Catalysis ,Epigenesis, Genetic ,Immunophenotyping ,Inorganic Chemistry ,Humans ,Amnion ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Cells, Cultured ,Gene Expression Profiling ,Organic Chemistry ,Computational Biology ,RNA sequencing ,Cell Differentiation ,Mesenchymal Stem Cells ,Molecular Sequence Annotation ,General Medicine ,MSC therapeutic properties ,Computer Science Applications ,Chemistry ,Gene Ontology ,MSC spheroids ,Gene Expression Regulation ,human amnion-derived mesenchymal stromal/stem cells ,3D priming ,regenerative medicine ,Human amnion-derived mesenchymal stromal/stem cells ,Transcriptome ,Biomarkers - Abstract
Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.
- Published
- 2022
13. Antihypertensive Peptides from Ultrafiltration and Fermentation of the Ricotta Cheese Exhausted Whey: Design and Characterization of a Functional Ricotta Cheese
- Author
-
Carlo Giuseppe Rizzello, Erica Pontonio, Marco Montemurro, Gina Valeria De Gennaro, Valerio Miceli, Pontonio, E., Montemurro, M., Gennaro, G. V. D., Miceli, V., and Rizzello, C. G.
- Subjects
Taste ,Health (social science) ,Fortification ,Ultrafiltration ,Plant Science ,TP1-1185 ,Health Professions (miscellaneous) ,Microbiology ,Article ,anti-ACE activity ,Starter ,Food science ,ricotta cheese exhausted whey ,fermentation ,Flavor ,Lactobacillus helveticus ,biology ,Chemistry ,Chemical technology ,food and beverages ,biology.organism_classification ,Chewiness ,Fermentation ,food by-products ,bioactive peptides ,Food Science - Abstract
Aiming at valorizing the ricotta cheese exhausted whey (RCEW), one of the most abundant by-products from the dairy industry, a biotechnological protocol to obtain bioactive peptides with angiotensin-I-converting enzyme (ACE)—inhibitory activity was set up. The approach was based on the combination of membrane filtration and fermentation. A Lactobacillus helveticus strain selected to be used as starter for the fermentation of the ultrafiltration protein-rich retentate (R-UF) obtained from RCEW. The fermented R-UF was characterized by a high anti-ACE activity. Peptides responsible for the bioactivity were purified and identified through nano-LC–ESI–MS/MS. The sequences identified in the purified active fractions of the fermented R-UF showed partial or complete overlapping with previously reported κ-casein antihypertensive fragments. The fermented R-UF was spray-dried and used to enrich ricotta cheese at different fortification level (1 and 5% w/w). An integrated approach including the assessment of the microbiological, chemical, functional, textural, and sensory properties was used to characterize the fortified products. A significantly higher anti-ACE activity was found in the ricotta cheese fortified with fermented R-UF as compared to the control and to the samples obtained with the unfermented R-UF fraction at the same levels of fortification. In particular, a 100 g portion of the ricotta cheese produced at 5% fortification level contained circa 30 mg of bioactive peptides. The fortification led to a moderate acidification, increased hardness and chewiness, and decreased the milk odor and taste of the ricotta cheese as compared to the control, while flavor persistence and sapidity improved.
- Published
- 2021
14. Amnion-Derived Mesenchymal Stromal/Stem Cell Paracrine Signals Potentiate Human Liver Organoid Differentiation: Translational Implications for Liver Regeneration
- Author
-
Antonio Lo Nigro, Alessia Gallo, Matteo Bulati, Giampiero Vitale, Diego Sebastian Paini, Mariangela Pampalone, Daniele Galvagno, Pier Giulio Conaldi, Vitale Miceli, Lo Nigro A., Gallo A., Bulati M., Vitale G., Paini D.S., Pampalone M., Galvagno D., Conaldi P.G., and Miceli V.
- Subjects
Medicine (General) ,Regeneration (biology) ,Mesenchymal stem cell ,General Medicine ,Biology ,Liver regeneration ,Transplantation ,Cell therapy ,3D liver organoid culture ,hepatocyte culture ,R5-920 ,Multipotent Stem Cell ,Cancer research ,Medicine ,hepatic progenitor cell differentiation ,Progenitor cell ,Stem cell ,liver regeneration ,human amnion-derived mesenchymal stem cells ,Original Research - Abstract
The prevalence of end-stage liver diseases has reached very high levels globally. The election treatment for affected patients is orthotopic liver transplantation, which is a very complex procedure, and due to the limited number of suitable organ donors, considerable research is being done on alternative therapeutic options. For instance, the use of cell therapy, such as the transplantation of hepatocytes to promote liver repair/regeneration, has been explored, but standardized protocols to produce suitable human hepatocytes are still limited. On the other hand, liver progenitor and multipotent stem cells offer potential cell sources that could be used clinically. Different studies have reported regarding the therapeutic effects of transplanted mesenchymal stromal/stem cells (MSCs) on end-stage liver diseases. Moreover, it has been shown that delivery of MSC-derived conditioned medium (MSC-CM) can reduce cell death and enhance liver proliferation in fulminant hepatic failure. Therefore, it is believed that MSC-CM contains many factors that probably support liver regeneration. In our work, we used an in vitro model of human liver organoids to study if the paracrine components secreted by human amnion-derived MSCs (hAMSCs) affected liver stem/progenitor cell differentiation. In particular, we differentiated liver organoids derived from bipotent EpCAM+ human liver cells and tested the effects of hAMSC secretome, derived from both two-dimensional (2D) and three-dimensional (3D) hAMSC cultures, on that model. Our analysis showed that conditioned medium (CM) produced by 3D hAMSCs was able to induce an over-expression of mature hepatocyte markers, such as ALB, NTCP, and CYP3A4, compared with both 2D hAMSC cultures and the conventional differentiation medium (DM). These data were confirmed by the over-production of ALB protein and over-activity of CYP3A4 observed in organoids grown in 3D hAMSC-CM. Liver repair dysfunction plays a role in the development of liver diseases, and effective repair likely requires the normal functioning of liver stem/progenitor cells. Herein, we showed that hAMSC-CM produced mainly by 3D cultures had the potential to increase hepatic stem/progenitor cell differentiation, demonstrating that soluble factors secreted by those cells are potentially responsible for the reaction. This work shows a potential approach to improve liver repair/regeneration also in a transplantation setting.
- Published
- 2021
15. A new nanocomposite packaging based on LASiS-generated AgNPs for the preservation of apple juice
- Author
-
Matteo Alessandro Del Nobile, Nicola Cioffi, Amalia Conte, Annalisa Volpe, Caterina Gaudiuso, Valerio Miceli, Maria Chiara Sportelli, Antonio Ancona, Valentina Lavicita, Sportelli, M. C., Ancona, A., Volpe, A., Gaudiuso, C., Lavicita, V., Miceli, V., Conte, A., Del Nobile, M. A., and Cioffi, Nicola
- Subjects
Microbiology (medical) ,Materials science ,Infrared spectroscopy ,02 engineering and technology ,RM1-950 ,Bacterial growth ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Microbiology ,Laser ablation synthesis in solution ,Silver nanoparticle ,Article ,Nanoantimicrobials ,Sustainable active packaging ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Spectroscopy ,chemistry.chemical_classification ,Nanocomposite ,Polymer ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Chemical state ,Infectious Diseases ,chemistry ,Chemical engineering ,Therapeutics. Pharmacology ,Silver nanoparticles ,0210 nano-technology ,Poly(-3-hydroxybutyrate-co-3-hydroxyvalerate) - Abstract
Designing bioactive materials, with controlled metal ion release, exerting a significant biological action and associated to low toxicity for humans, is nowadays one of the most important challenges for our community. The most looked-for nanoantimicrobials are capable of releasing metal species with defined kinetic profiles, either by slowing down or inhibiting bacterial growth and pathogenic microorganism diffusion. In this study, laser ablation synthesis in solution (LASiS) has been used to produce bioactive Ag-based nanocolloids, in isopropyl alcohol, which can be used as water-insoluble nano-reservoirs in composite materials like poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Infrared spectroscopy was used to evaluate the chemical state of pristine polymer and final composite material, thus providing useful information about synthesis processes, as well as storage and processing conditions. Transmission electron microscopy was exploited to study the morphology of nano-colloids, along with UV-Vis for bulk chemical characterization, highlighting the presence of spheroidal particles with average diameter around 12 nm. Electro-thermal atomic absorption spectroscopy was used to investigate metal ion release from Ag-modified products, showing a maximum release around 60 ppb, which ensures an efficient antimicrobial activity, being much lower than what recommended by health institutions. Analytical spectroscopy results were matched with bioactivity tests carried out on target microorganisms of food spoilage.
- Published
- 2021
16. The Immunomodulatory Properties of the Human Amnion-Derived Mesenchymal Stromal/Stem Cells Are Induced by INF-γ Produced by Activated Lymphomonocytes and Are Mediated by Cell-To-Cell Contact and Soluble Factors
- Author
-
Matteo Bulati, Vitale Miceli, Alessia Gallo, Giandomenico Amico, Claudia Carcione, Mariangela Pampalone, Pier Giulio Conaldi, Bulati M., Miceli V., Gallo A., Amico G., Carcione C., Pampalone M., and Conaldi P.G.
- Subjects
0301 basic medicine ,Programmed Cell Death 1 Receptor ,Cell Communication ,Lymphocyte Activation ,immunomodulation ,B7-H1 Antigen ,Monocytes ,0302 clinical medicine ,Immunology and Allergy ,Original Research ,Chemistry ,Cell Differentiation ,Healthy Volunteers ,I-kappa B Kinase ,Cell biology ,medicine.anatomical_structure ,primed-hAMSCs ,Monocyte differentiation ,Cytokines ,Stem cell ,lcsh:Immunologic diseases. Allergy ,Stromal cell ,T cell ,Primary Cell Culture ,Immunology ,regenerative medicine ,exosomes ,Interferon-gamma ,03 medical and health sciences ,Paracrine signalling ,Immune system ,interferon-γ ,medicine ,Humans ,Immunologic Factors ,Amnion ,human amnion-derived mesenchymal stem cells ,Cell Proliferation ,Immunosuppression Therapy ,PDL-1 ,Mesenchymal stem cell ,Immunity ,M2-like monocytes ,Mesenchymal Stem Cells ,Coculture Techniques ,Microvesicles ,MicroRNAs ,030104 developmental biology ,Leukocytes, Mononuclear ,lcsh:RC581-607 ,Interferon Regulatory Factor-1 ,030215 immunology - Abstract
Human mesenchymal stromal/stem cells (MSCs), being immunoprivileged and having immunomodulatory ability, represent a promising tool to be applied in the field of regenerative medicine. Based on numerous in vitro evidences, the immunological effects of MSCs on immune cells could depend on different mechanisms as cell-to-cell contact and paracrine signals. Furthermore, recent studies have shown that the immunomodulatory activity of MSCs is initiated by activated immune cells; thus, their interaction represents a potential homeostatic mechanism by which MSCs regulate the immune response. MSCs also release exosomes able to give different effects, in a paracrine manner, by influencing inflammatory processes. In this study, we aimed to establish the potential role of human amnion-derived MSCs (hAMSCs), in immunomodulation. We found that the immunosuppressive properties of hAMSCs are not constitutive, but require “supportive signals” capable of promoting these properties. Indeed, we observed that hAMSCs alone are not able to produce an adequate amount of soluble immunomodulatory factors. Here, we studied, in depth, the strong immunomodulatory licensing signal deriving from the direct interaction between hAMSCs and stimulated peripheral blood mononuclear cells. We found that the immunomodulatory effect of hAMSCs also depends on cell-to-cell contact through the contribution of the PDL-1/PD-1 axis. We then investigated the IFN-γ priming of hAMSCs (γ-hAMSCs), which induce the increase of PDL-1 expression, high production of IDO, and upregulation of different immunomodulatory exosome-derived miRNAs. Our miRNA–target network analysis revealed that nine of the deregulated miRNAs are involved in the regulation of key proteins that control both T cell activation/anergy and monocyte differentiation pathways. Finally, we observed that γ-hAMSCs induce in monocytes both M2-like phenotype and the increase of IL-10 production. The extensive implications of MSCs in modulating different aspects of the immune system make these cells attractive candidates to be employed in therapeutic application in immune-based diseases. For these reasons, we aimed, with this study, to shed light on the potential of hAMSCs, and how they could become a useful tool for treating different inflammatory diseases, including end-stage pathologies or adverse effects in transplanted patients.
- Published
- 2020
17. Comparative study of the production of soluble factors in human placenta-derived mesenchymal stromal/stem cells grown in adherent conditions or as aggregates in a catheter-like device
- Author
-
Vitale Miceli, Pier Giulio Conaldi, Mariangela Pampalone, Cinzia Maria Chinnici, Eva Schmelzer, Jörg C. Gerlach, Giandomenico Amico, Matteo Bulati, Miceli V., Chinnici C.M., Bulati M., Pampalone M., Amico G., Schmelzer E., Gerlach J.C., and Conaldi P.G.
- Subjects
0301 basic medicine ,Stromal cell ,Angiogenesis ,Cell Survival ,Placenta ,Cell ,Biophysics ,Cell Culture Techniques ,Biocompatible Materials ,Biology ,Paracrine effects ,Biochemistry ,Regenerative medicine ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Movement ,Pregnancy ,medicine ,Cell Adhesion ,Human Umbilical Vein Endothelial Cells ,Humans ,Immunologic Factors ,Amnion ,Molecular Biology ,Cell Aggregation ,Settore MED/04 - Patologia Generale ,Catheter-like device ,Placenta-derived stromal/stem cells ,Settore BIO/16 - Anatomia Umana ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,Cells, Immobilized ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Angiogenesis Inducing Agents ,Female ,Stem cell ,Adult stem cell - Abstract
Different approaches have been studied in both preclinical and clinical settings to develop cell-based therapies and/or engineered cell-based therapies to better integrate grafts with the host. In these techniques, much attention is addressed to the use of adult stem cells such as mesenchymal stem cells (MSCs), but identifying and obtaining sufficient numbers of therapeutic cells, and the right route of administration, is often a challenge. In this study, we tested the feasibility of encapsulating human amnion-derived MSCs (hAMSCs) in a semipermeable and biocompatible fiber as a new approach for regenerative medicine. Our data showed that hAMSCs aggregated in the device constitutes an effective system for enhancing, or at least for maintaining, the paracrine activity of these cells in order to better promote tissue regeneration in an immune isolated state. In our new experimental approach, the hAMSCs retained their therapeutic potential, as shown by both the production of specific immunomodulatory/angiogenic factors and immunomodulatory and angiogenic ability observed in vitro. Unlike cell infusion methods, the use of encapsulated-cells leads to minimally invasive approaches, avoiding a direct interaction with the host. Therefore, the potentiality of an allograft or xenograft without the need for immunosuppression, and the lack of tumorigenesis is very intriguing.
- Published
- 2020
18. Role of non-coding RNAs in age-related vascular cognitive impairment: An overview on diagnostic/prognostic value in Vascular Dementia and Vascular Parkinsonism
- Author
-
Alessia Gallo, Pier Giulio Conaldi, V. Lo Re, Vitale Miceli, Gianvincenzo Sparacia, Valentina Agnese, Matteo Bulati, Gioacchin Iannolo, Giovanna Russelli, Miceli V., Russelli G., Iannolo G., Gallo A., Lo Re V., Agnese V., Sparacia G., Conaldi P.G., and Bulati M.
- Subjects
0301 basic medicine ,Aging ,RNA, Untranslated ,Endothelium ,Heart disease ,Vascular Parkinsonism ,Vascular Dementia ,Bioinformatics ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Parkinsonian Disorders ,medicine ,Dementia ,Humans ,Cognitive Dysfunction ,Endothelial dysfunction ,Vascular dementia ,Stroke ,business.industry ,Parkinsonism ,Dementia, Vascular ,Vascular ageing ,medicine.disease ,ncRNA ,030104 developmental biology ,medicine.anatomical_structure ,Blood brain barrier ,Cerebrovascular Circulation ,business ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Age is the pivotal risk factor for different common medical conditions such as cardiovascular diseases, cancer and dementia. Among age-related disorders, cardiovascular and cerebrovascular diseases, represent the leading causes of premature mortality strictly related to vascular ageing, a pathological condition characterized by endothelial dysfunction, atherosclerosis, hypertension, heart disease and stroke. These features negatively impact on the brain, owing to altered cerebral blood flow, neurovascular coupling and impaired endothelial permeability leading to cerebrovascular diseases (CVDs) as Vascular Dementia (VD) and Parkinsonism (VP). It is an increasing opinion that neurodegenerative disorders and cerebrovascular diseases are associated from a pathogenetic point of view, and in this review, we discuss how cerebrovascular dysfunctions, due to epigenetic alterations, are linked with neuronal degeneration/dysfunction that lead to cognitive impairment. The relation between neurodegenerative and cerebrovascular diseases are reviewed with a focus on role of ncRNAs in age-related vascular diseases impairing the endothelium in the blood-brain barrier with consequent dysfunction of cerebral blood flow. In this review we dissert about different regulatory mechanisms of gene expression implemented by ncRNAs in the pathogenesis of age-related neurovascular impairment, aiming to highlight the potential use of ncRNAs as biomarkers for diagnostic/prognostic purposes as well as novel therapeutic targets.
- Published
- 2020
19. Perinatal and newborn care in a two years retrospective study in a first level peripheral hospital in Sicily (Italy)
- Author
-
Gregorio Serra, Salvatore Albano, Vincenzo Miceli, Giovanni Corsello, and Serra G, Miceli V, Albano S, Corsello G
- Subjects
Adult ,Patient Transfer ,medicine.medical_specialty ,Complications of pregnancy ,Adolescent ,Term Birth ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Health care ,medicine ,Humans ,Childbirth ,030212 general & internal medicine ,Retrospective Studies ,Perinatal mortality ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Research ,Public health ,Infant, Newborn ,Quality of care ,lcsh:RJ1-570 ,Gestational age ,lcsh:Pediatrics ,Retrospective cohort study ,Middle Aged ,Stillbirth ,Delivery, Obstetric ,Newborn ,medicine.disease ,Infant Formula ,Obstetric Labor Complications ,Perinatal Care ,Breast Feeding ,Italy ,Premature Birth ,Female ,Maternal death ,business - Abstract
Background Two hundred seventy-five thousand maternal deaths, 2.7 million neonatal deaths, and 2.6 million stillbirths have been estimated in 2015 worldwide, almost all in low-income countries (LICs). Moreover, more than 20 million severe disabilities result from the complications of pregnancy, childbirth or its management each year. A significant decrease of mortality/morbidity rates could be achieved by providing effective perinatal and newborn care also in high-income countries (HICs), especially in peripheral hospitals and/or rural areas, where the number of childbirths per year is often under the minimal threshold recognized by the reference legislation. We report on a 2 years retrospective cohort study, conducted in a first level peripheral hospital in Cefalù, a small city in Sicily (Italy), to evaluate care provided and mortality/morbidity rates. The proposed goal is to improve the quality of care, and the services that peripheral centers can offer. Methods We collected data from maternity and neonatal records, over a 2-year period from January 2017 to December 2018. The informations analyzed were related to demographic features (age, ethnicity/origin area, residence, educational level, marital status), diagnosis at admission (attendance of birth training courses, parity, type of pregnancy, gestational age, fetal presentation), mode of delivery, obstetric complications, the weight of the newborns, their feeding and eventual transfer to II level hospitals, also through the Neonatal Emergency Transport Service, if the established criteria were present. Results Eight hundred sixteen women were included (age 18–48 years). 179 (22%) attended birth training courses. 763 (93%) were Italian, 53 foreign (7%). 175 (21%) came from outside the province of Palermo. Eight hundred ten were single pregnancies, 6 bigeminal; 783 were at term (96%), 33 preterm (4%, GA 30–41 WG); 434 vaginal deliveries (53%), 382 caesarean sections (47%). One maternal death and 28 (3%) obstetric complications occurred during the study period. The total number of children born to these women was 822, 3 of which stillbirths (3.6‰). 787 (96%) were born at term (>37WG), 35 preterm (4%), 31 of which late preterm. Twenty-one newborns (2.5%) were transferred to II level hospitals. Among them, 3 for moderate/severe prematurity, 18 for mild prematurity/other pathology. The outcome was favorable for all women (except 1 hysterectomy) and the newborns transferred, and no neonatal deaths occurred in the biennium under investigation. Of the remaining 798 newborns, 440 were breastfed at discharge (55%), 337 had a mixed feeding (breastfed/formula fed, 42%) and 21 were formula fed (3%). Conclusions Although the minimal standard of adequate perinatal care in Italy is >500 childbirths/year, the aims of the Italian legislation concern the rationalization of birth centers as well as the structural, technological and organizational improvement of health facilities. Therefore, specific contexts and critical areas need to be identified and managed. Adequate resources and intervention strategies should be addressed not only to perinatal emergencies, but also to the management of mild prematurity/pathology, especially in vulnerable populations for social or orographic reasons. The increasing availability and spread of health care offers, even in HICs, cannot be separated from the goal of quality of care, which is an ethic and public health imperative.
- Published
- 2019
20. In vitro evidences of epithelial to mesenchymal transition in low cell-density cultured human fetal hepatocytes
- Author
-
Cinzia Maria Chinnici, Vitale Miceli, Antonio Lo Nigro, Mariangela Pampalone, Giandomenico Amico, Pier Giulio Conaldi, Chinnici C.M., Miceli V., Pampalone M., Lo Nigro A., Amico G., and Conaldi P.G.
- Subjects
Liver Cirrhosis ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,Liver fibrosis ,Cell Culture Techniques ,Biophysics ,Cell Count ,Biology ,Primary cultures ,Biochemistry ,03 medical and health sciences ,Fetal hepatocytes ,medicine ,Humans ,Epithelial–mesenchymal transition ,Molecular Biology ,Gene ,Cells, Cultured ,Epithelial to mesenchymal transition ,Fetus ,Transition (genetics) ,Cell Biology ,Phenotype ,In vitro ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,Hepatocyte ,Immunology ,Hepatocytes - Abstract
Culturing fetal hepatocytes in high cell-density allowed stabilization of the hepatocyte phenotype up to 8 weeks, including the maintenance of liver-specific functions. On the other hand, when cultured at low cell-density, fetal hepatocytes underwent morphological modifications and acquired fibroblastic morphology. Since a switch from E-cadherin to vimentin expression accompanied these changes, we hypothesized the occurrence of epithelial-to-mesenchymal transition when fetal hepatocytes were cultured at low cell-density. Changes in gene expressionsuch as up-regulation of fibrosis-related geneswere also observed, suggesting that the low cell-density culture system promoted the acquisition of a profibrotic phenotype in cultured hepatocytes. The origin of fibrogenic cells in the liver is not well known, and the role of hepatocytes as a source of fibrogenic cells is controversial. Therefore, we hypothesized that hepatocytes undergoing epithelial-to-mesenchymal transition could have a central role in liver fibrosis as a source of fibrogenic cells. To conclude, the high cell-density culture system could be a useful model for in vitro studies requiring long-term cultures of hepatocytes, such as the development of pharmaceutical drugs and mechanisms of viral infections. The low cell-density culture system may provide additional insights into the origin of fibrogenic cells in the liver, thus contributing to the development of novel therapeutic approaches.
- Published
- 2017
21. Comparison of Immunosuppressive and Angiogenic Properties of Human Amnion-Derived Mesenchymal Stem Cells between 2D and 3D Culture Systems
- Author
-
Pier Giulio Conaldi, Serena Vella, Mariangela Pampalone, Giandomenico Amico, Anna Paola Carreca, Vitale Miceli, Miceli V., Pampalone M., Vella S., Carreca A.P., Amico G., and Conaldi P.G.
- Subjects
lcsh:Internal medicine ,Amnion ,Article Subject ,Regeneration (biology) ,Mesenchymal stem cell ,Cell Biology ,Biology ,Regenerative medicine ,Microvesicles ,In vitro ,Cell biology ,Paracrine signalling ,medicine.anatomical_structure ,human amnion-derived mesenchymal stem cell ,medicine ,lcsh:RC31-1245 ,Molecular Biology ,Transcription factor ,Research Article - Abstract
The secretion of potential therapeutic factors by mesenchymal stem cells (MSCs) has aroused much interest given the benefits that it can bring in the field of regenerative medicine. Indeed, the in vitro multipotency of these cells and the secretive capacity of both angiogenic and immunomodulatory factors suggest a role in tissue repair and regeneration. However, during culture, MSCs rapidly lose the expression of key transcription factors associated with multipotency and self-renewal, as well as the ability to produce functional paracrine factors. In our study, we show that a three-dimensional (3D) culture method is effective to induce MSC spheroid formation, to maintain the multipotency and to improve the paracrine activity of a specific population of human amnion-derived MSCs (hAMSCs). The regenerative potential of both 3D culture-derived conditioned medium (3D CM) and their exosomes (EXO) was assessed against 2D culture products. In particular, tubulogenesis assays revealed increased capillary maturation in the presence of 3D CM compared with both 2D CM and 2D EXO. Furthermore, 3D CM had a greater effect on inhibition of PBMC proliferation than both 2D CM and 2D EXO. To support this data, hAMSC spheroids kept in our 3D culture system remained viable and multipotent and secreted considerable amounts of both angiogenic and immunosuppressive factors, which were detected at lower levels in 2D cultures. This work reveals the placenta as an important source of MSCs that can be used for eventual clinical applications as cell-free therapies.
- Published
- 2019
22. Production of the Polyhydroxyalkanoate PHBV from Ricotta Cheese Exhausted Whey by Haloferax mediterranei Fermentation
- Author
-
Valerio Miceli, Marco Montemurro, Carlo Giuseppe Rizzello, Susanna Raho, Domenico Centrone, Monica Schioppa, Paolo Stufano, Erica Pontonio, Vito Emanuele Carofiglio, Raho, S., Carofiglio, V. E., Montemurro, M., Miceli, V., Centrone, D., Stufano, P., Schioppa, M., Pontonio, E., and Rizzello, C. G.
- Subjects
Health (social science) ,PHA ,whey ,02 engineering and technology ,Plant Science ,Fractionation ,lcsh:Chemical technology ,Health Professions (miscellaneous) ,Microbiology ,Bioplastic ,Polyhydroxyalkanoates ,03 medical and health sciences ,chemistry.chemical_compound ,Differential scanning calorimetry ,bioplastic ,Haloferax ,ricotta cheese exhausted whey ,Bioreactor ,lcsh:TP1-1185 ,Food science ,Lactose ,030304 developmental biology ,0303 health sciences ,021001 nanoscience & nanotechnology ,Haloferax mediterranei ,chemistry ,Fermentation ,0210 nano-technology ,Food Science - Abstract
In the last decade, the dairy industry underwent a rapid expansion due to the increasing demand of milk-based products, resulting in high quantity of wastewater, i.e., whey and ricotta cheese exhausted whey (RCEW). Although containing high content of nutritional compounds, dairy by-products are still disposed as waste rather being reintroduced in a new production chain, hence leading to environmental and economic issues. This study proposes a new biotechnological approach based on the combination of membrane filtration and fermentation to produce poly-hydroxyalkanoates (PHA), biodegradable bioplastics candidate as an alternative to petroleum-derived plastics. The protocol, exploiting the metabolic capability Haloferax mediterranei to synthesize PHA from RCEW carbon sources, was set up under laboratory and pilot scale conditions. A multi-step fractionation was used to recover a RCEW fraction containing 12.6% (w/v) of lactose, then subjected to an enzymatic treatment aimed at releasing glucose and galactose. Fermentation conditions (culture medium for the microorganism propagation, inoculum size, time, and temperature of incubation) were selected according to the maximization of polymer synthesis, under in-flasks experiments. The PHA production was then tested using a bioreactor system, under stable and monitored pH, temperature, and stirring conditions. The amount of the polymer recovered corresponded to 1.18 g/L. The differential scanning calorimetry (DSC) analysis revealed the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as the polymer synthesized, with a relatively high presence of hydroxyvalerate (HV). Identity and purity of the polymer were confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopy analyses. By combining the fractionation of RCEW, one of the most abundant by-products from the agri-food industry, and the use of the halophile Hfx mediterranei, the production of PHBV with high purity and low crystallinity has successfully been optimized. The process, tested up to pilot scale conditions, may be further implemented (e.g., through fed-batch systems) and used for large-scale production of bioplastics, reducing the economical and environmental issues related the RCEW disposal.
- Published
- 2020
23. Carnosine protects pancreatic beta cells and islets against oxidative stress damage
- Author
-
Giovanna Frazziano, Vitale Miceli, Giuseppe Grasso, Camillo Ricordi, Mariangela Pampalone, Pier Giulio Conaldi, Gioacchin Iannolo, Enrico Rizzarelli, Anna Casu, Miceli V., Pampalone M., Frazziano G., Grasso G., Rizzarelli E., Ricordi C., Casu A., Iannolo G., and Conaldi P.G.
- Subjects
0301 basic medicine ,Nitrous Oxide ,Carnosine ,Apoptosis ,medicine.disease_cause ,Biochemistry ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Endocrinology ,Insulin-Secreting Cells ,Insulin Secretion ,geography.geographical_feature_category ,Chemistry ,Nitrotyrosine ,Diabetes ,Islet ,Reactive Nitrogen Species ,medicine.anatomical_structure ,Beta cell ,Pancreatic islet transplantation ,medicine.medical_specialty ,Cell Survival ,Protective Agents ,Cell Line ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Molecular Biology ,Beta cell line ,Cell Shape ,Cell Proliferation ,Settore MED/04 - Patologia Generale ,geography ,Pancreatic islets ,Transcription Factor RelA ,Hydrogen Peroxide ,Rats ,Transplantation ,Oxidative Stress ,030104 developmental biology ,Glucose ,Gene Expression Regulation ,Cytoprotection ,Tyrosine ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress ,Biomarkers - Abstract
Islet transplantation is a valid therapeutic option for type 1 diabetes treatment. However, in this procedure one of the major problems is the oxidative stress produced during pancreatic islet isolation. The aim of our study was to evaluate potential protective effects of L-carnosine and its isomer D-carnosine against oxidative stress. We evaluated the carnosine effect on cell growth, cell death, insulin production, and the main markers of oxidative stress in rat and murine stressed beta cell lines as well as in human pancreatic islets. Both isomers clearly inhibited hydrogen peroxide induced cytotoxicity, with a decrease in intracellular reactive oxygen and nitrogen species, prevented hydrogen peroxide induced apoptosis/necrosis, nitrite production, and reduced glucose-induced insulin secretion. In addition, NF-κB expression/translocation and nitrated protein induced in stressed cells was significantly reduced. Furthermore, both isomers improved survival and function, and decreased reactive oxygen and nitrogen species, and nitrite and nitrotyrosine production in human islets cultured for 1, 3, and 7 days. These results seem to indicate that both L and D-carnosine have a significant cytoprotective effect by reducing oxidative stress in beta cell lines and human islets, suggesting their potential use to improve islet survival during the islet transplantation procedure.
- Published
- 2018
24. Comments on "Bile Chemistry During Ex Situ Normothermic Liver Perfusion Does Not Always Predict Cholangiopathy".
- Author
-
Miceli V, Dos Santos Barata E, De Roover A, Olivier D, and Gilbo N
- Subjects
- Humans, Liver blood supply, Organ Preservation methods, Predictive Value of Tests, Liver Transplantation, Perfusion methods, Bile metabolism
- Abstract
Competing Interests: The authors declare no funding or conflicts of interest.
- Published
- 2024
- Full Text
- View/download PDF
25. Native characterization and QC profiling of human amniotic mesenchymal stromal cell vesicular fractions for secretome-based therapy.
- Author
-
Marassi V, La Rocca G, Placci A, Muntiu A, Vincenzoni F, Vitali A, Desiderio C, Maraldi T, Beretti F, Russo E, Miceli V, Conaldi PG, Papait A, Romele P, Cargnoni A, Silini AR, Alviano F, Parolini O, Giordani S, Zattoni A, Reschiglian P, and Roda B
- Subjects
- Humans, Quality Control, Cells, Cultured, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Secretome metabolism, Amnion chemistry, Amnion cytology, Amnion metabolism, Extracellular Vesicles chemistry, Extracellular Vesicles metabolism
- Abstract
Human amniotic mesenchymal stromal cells (hAMSCs) have unique immunomodulatory properties making them attractive candidates for regenerative applications in inflammatory diseases. Most of their beneficial properties are mediated through their secretome. The bioactive factors concurring to its therapeutic activity are still unknown. Evidence suggests synergy between the two main components of the secretome, soluble factors and vesicular fractions, pivotal in shifting inflammation and promoting self-healing. Biological variability and the absence of quality control (QC) protocols hinder secretome-based therapy translation to clinical applications. Moreover, vesicular secretome contains a multitude of particles with varying size, cargos and functions whose complexity hinders full characterization and comprehension. This study achieved a significant advancement in secretome characterization by utilizing native, FFF-based separation and characterizing extracellular vesicles derived from hAMSCs. This was accomplished by obtaining dimensionally homogeneous fractions then characterized based on their protein content, potentially enabling the identification of subpopulations with diverse functionalities. This method proved to be successful as an independent technique for secretome profiling, with the potential to contribute to the standardization of a qualitative method. Additionally, it served as a preparative separation tool, streamlining populations before ELISA and LC-MS characterization. This approach facilitated the categorization of distinctive and recurring proteins, along with the identification of clusters associated with vesicle activity and functions. However, the presence of proteins unique to each fraction obtained through the FFF separation tool presents a challenge for further analysis of the protein content within these cargoes., Competing Interests: Funding The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Ornella Parolini reports financial support was provided by PRIN 2017 program of Italian Ministry of Research and University (MIUR, Grant No. 2017RSAFK7). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
26. The performance of the node reporting and data system 1.0 (Node-RADS) and DWI-MRI in staging patients with cervical carcinoma according to the new FIGO classification (2018).
- Author
-
Ninkova RV, Calabrese A, Curti F, Riccardi S, Gennarini M, Miceli V, Cupertino A, Di Donato V, Pernazza A, Rizzo SM, Panebianco V, Catalano C, and Manganaro L
- Subjects
- Humans, Female, Middle Aged, Retrospective Studies, Adult, Aged, Lymph Nodes diagnostic imaging, Lymph Nodes pathology, Predictive Value of Tests, Uterine Cervical Neoplasms diagnostic imaging, Uterine Cervical Neoplasms pathology, Diffusion Magnetic Resonance Imaging methods, Neoplasm Staging, Lymphatic Metastasis diagnostic imaging, Sensitivity and Specificity
- Abstract
Purpose: To evaluate the diagnostic accuracy of the Node-RADS score and the utility of apparent diffusion coefficient (ADC) values in predicting metastatic lymph nodes (LNs) involvement in cervical cancer (CC) patients using magnetic resonance imaging (MRI). The applicability of the Node RADS score across three readers with different years of experience in pelvic imaging was also assessed., Material and Methods: Among 140 patients, 68 underwent staging MRI, neoadjuvant chemotherapy and radical surgery, forming the study cohort. Node-RADS scores of the main pelvic stations were retrospectively determined to assess LN metastatic likelihood and compared with the histological findings. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of LNs classified as Node-RADS ≥ 3 were measured and compared with histological reports, considered as gold standard., Results: Sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and accuracy were calculated for different Node-RADS thresholds. Node RADS ≥ 3 showed a sensitivity of 92.8% and specificity of 72.5%. Node RADS ≥ 4 yielded a sensitivity of 71.4% and specificity of 100%, while Node RADS 5 yielded 42.9% and 100%, respectively. The diagnostic performance of mean ADC, cADC and rADC values from 78 LNs with Node-RADS score ≥ 3 was assessed, with ADC demonstrating the highest area under the curve (AUC 0.820), compared to cADC and rADC values., Conclusion: The Node-RADS score provides a standardized LNs assessment, enhancing diagnostic accuracy in CC patients. Its ease of use and high inter-observer concordance support its clinical utility. ADC measurement of LNs shows promise as an additional tool for optimizing patient diagnostic evaluation., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
27. Proteomic analysis and functional validation reveal distinct therapeutic capabilities related to priming of mesenchymal stromal/stem cells with IFN-γ and hypoxia: potential implications for their clinical use.
- Author
-
Calligaris M, Zito G, Busà R, Bulati M, Iannolo G, Gallo A, Carreca AP, Cuscino N, Castelbuono S, Carcione C, Centi C, Amico G, Bertani A, Chinnici CM, Conaldi PG, Scilabra SD, and Miceli V
- Abstract
Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Calligaris, Zito, Busà, Bulati, Iannolo, Gallo, Carreca, Cuscino, Castelbuono, Carcione, Centi, Amico, Bertani, Chinnici, Conaldi, Scilabra and Miceli.)
- Published
- 2024
- Full Text
- View/download PDF
28. Extracellular Vesicles in Lung Cancer: Implementation in Diagnosis and Therapeutic Perspectives.
- Author
-
Carreca AP, Tinnirello R, Miceli V, Galvano A, Gristina V, Incorvaia L, Pampalone M, Taverna S, and Iannolo G
- Abstract
Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell-cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer., Competing Interests: The authors declare no conflicts of interest.
- Published
- 2024
- Full Text
- View/download PDF
29. Use of priming strategies to advance the clinical application of mesenchymal stromal/stem cell-based therapy.
- Author
-
Miceli V
- Abstract
Mesenchymal stromal/stem cells (MSCs) have garnered significant attention in the field of regenerative medicine due to their remarkable therapeutic potential. MSCs play a pivotal role in maintaining tissue homeostasis and possess diverse functions in tissue repair and recovery in various organs. These cells are characterized by easy accessibility, few ethical concerns, and adaptability to in vitro cultures, making them a valuable resource for cell therapy in several clinical conditions. Over the years, it has been shown that the true therapeutic power of MSCs lies not in cell engraftment and replacement but in their ability to produce critical paracrine factors, including cytokines, growth factors, and exosomes (EXOs), which modulate the tissue microenvironment and facilitate repair and regeneration processes. Consequently, MSC-derived products, such as conditioned media and EXOs, are now being extensively evaluated for their potential medical applications, offering advantages over the long-term use of whole MSCs. However, the efficacy of MSC-based treatments varies in clinical trials due to both intrinsic differences resulting from the choice of diverse cell sources and non-standardized production methods. To address these concerns and to enhance MSC therapeutic potential, researchers have explored many priming strategies, including exposure to inflammatory molecules, hypoxic conditions, and three-dimensional culture techniques. These approaches have optimized MSC secretion of functional factors, empowering them with enhanced immunomodulatory, angiogenic, and regenerative properties tailored to specific medical conditions. In fact, various priming strategies show promise in the treatment of numerous diseases, from immune-related disorders to acute injuries and cancer. Currently, in order to exploit the full therapeutic potential of MSC therapy, the most important challenge is to optimize the modulation of MSCs to obtain adapted cell therapy for specific clinical disorders. In other words, to unlock the complete potential of MSCs in regenerative medicine, it is crucial to identify the most suitable tissue source and develop in vitro manipulation protocols specific to the type of disease being treated., Competing Interests: Conflict-of-interest statement: The author reported no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
30. Imaging of Peritoneal Carcinomatosis in Advanced Ovarian Cancer: CT, MRI, Radiomic Features and Resectability Criteria.
- Author
-
Miceli V, Gennarini M, Tomao F, Cupertino A, Lombardo D, Palaia I, Curti F, Riccardi S, Ninkova R, Maccioni F, Ricci P, Catalano C, Rizzo SMR, and Manganaro L
- Abstract
PC represents the most striking picture of the loco-regional spread of ovarian cancer, configuring stage III. In the last few years, many papers have evaluated the role of imaging and therapeutic management in patients with ovarian cancer and PC. This paper summed up the literature on traditional approaches to the imaging of peritoneal carcinomatosis in advanced ovarian cancer, presenting classification systems, most frequent patterns, routes of spread and sites that are difficult to identify. The role of imaging in diagnosis was investigated, with particular attention to the reported sensitivity and specificity data-computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT)-and to the peritoneal cancer index (PCI). In addition, we explored the therapeutic possibilities and radiomics applications that can impact management of patients with ovarian cancer. Careful staging is mandatory, and patient selection is one of the most important factors influencing complete cytoreduction (CCR) outcome: an accurate pre-operative imaging may allow selection of patients that may benefit most from primary cytoreductive surgery.
- Published
- 2023
- Full Text
- View/download PDF
31. Oncolytic Effect of Zika Virus in Neuroendocrine Pancreatic Tumors: New Perspectives for Therapeutic Approaches.
- Author
-
Cocco MM, Carcione C, Miceli V, Tinnirello R, Chinnici CM, Carbone C, Zito G, Conaldi PG, and Iannolo G
- Subjects
- Adult, Humans, Pancreatic Hormones, Zika Virus physiology, Oncolytic Virotherapy, Glioblastoma therapy, Zika Virus Infection, Neuroendocrine Tumors pathology, Pancreatic Neoplasms pathology, Oncolytic Viruses
- Abstract
Pancreatic cancer (PCa) is the fifth leading cause of cancer mortality. Recently, our group and others have demonstrated the oncolytic activity of the Zika virus (ZIKV) against glioblastoma. The peculiar features of this virus offer the opportunity to use an agent already tested in vivo through natural transmission, with minimal effects on adults, to specifically target a tumor such as glioblastoma. This remarkable specificity prompted us to explore the potential use of ZIKV oncolytic action against other tumor types. In particular, we focused on the subgroup of pancreatic tumors with a neuroendocrine origin known as neuroendocrine tumors (NETs). We found that ZIKV exerts its oncolytic activity by specifically infecting NET cells, leading to growth inhibition and cell death. We also assessed whether the oncolytic action could be extended to pancreatic tumors different from NETs. However, as expected, the viral specificity is limited to NETs and is not applicable to adenocarcinoma tumors, indicating a narrow spectrum of action for this virus. These findings support the potential use of ZIKV in therapeutic approaches not only in glioblastoma, but also against other tumors, such as neuroendocrine pancreatic tumors.
- Published
- 2023
- Full Text
- View/download PDF
32. The Truth Is Out There: Biological Features and Clinical Indications of Extracellular Vesicles from Human Perinatal Stem Cells.
- Author
-
Russo E, Alberti G, Corrao S, Borlongan CV, Miceli V, Conaldi PG, Di Gaudio F, and La Rocca G
- Subjects
- Pregnancy, Female, Humans, Regenerative Medicine methods, Wound Healing, Wharton Jelly, Mesenchymal Stem Cells, Extracellular Vesicles physiology
- Abstract
The potential of perinatal tissues to provide cellular populations to be used in different applications of regenerative medicine is well established. Recently, the efforts of researchers are being addressed regarding the evaluation of cell products (secreted molecules or extracellular vesicles, EVs) to be used as an alternative to cellular infusion. The data regarding the effective recapitulation of most perinatal cells' properties by their secreted complement point in this direction. EVs secreted from perinatal cells exhibit key therapeutic effects such as tissue repair and regeneration, the suppression of inflammatory responses, immune system modulation, and a variety of other functions. Although the properties of EVs from perinatal derivatives and their significant potential for therapeutic success are amply recognized, several challenges still remain that need to be addressed. In the present review, we provide an up-to-date analysis of the most recent results in the field, which can be addressed in future research in order to overcome the challenges that are still present in the characterization and utilization of the secreted complement of perinatal cells and, in particular, mesenchymal stromal cells.
- Published
- 2023
- Full Text
- View/download PDF
33. Two Sides of The Same Coin: Normal and Tumoral Stem Cells, The Relevance of In Vitro Models and Therapeutic Approaches: The Experience with Zika Virus in Nervous System Development and Glioblastoma Treatment.
- Author
-
Tinnirello R, Chinnici CM, Miceli V, Busà R, Bulati M, Gallo A, Zito G, Conaldi PG, and Iannolo G
- Subjects
- Adult, Humans, Animals, Mice, Neoplastic Stem Cells, Brain, Glioblastoma therapy, Zika Virus, Zika Virus Infection
- Abstract
Neural stem cells (NSCs) were described for the first time more than two decades ago for their ability to differentiate into all neural cell lineages. The isolation of NSCs from adults and embryos was carried out by various laboratories and in different species, from mice to humans. Similarly, no more than two decades ago, cancer stem cells were described. Cancer stem cells, previously identified in hematological malignancies, have now been isolated from several solid tumors (breast, brain, and gastrointestinal compartment). Though the origin of these cells is still unknown, there is a wide consensus about their role in tumor onset, propagation and, in particular, resistance to treatments. Normal and neoplastic neural stem cells share common characteristics, and can thus be considered as two sides of the same coin. This is particularly true in the case of the Zika virus (ZIKV), which has been described as an inhibitor of neural development by specifically targeting NSCs. This understanding prompted us and other groups to evaluate ZIKV action in glioblastoma stem cells (GSCs). The results indicate an oncolytic activity of this virus vs. GSCs, opening potentially new possibilities in glioblastoma treatment.
- Published
- 2023
- Full Text
- View/download PDF
34. Fetal MRI: what's new? A short review.
- Author
-
Manganaro L, Capuani S, Gennarini M, Miceli V, Ninkova R, Balba I, Galea N, Cupertino A, Maiuro A, Ercolani G, and Catalano C
- Subjects
- Pregnancy, Female, Humans, Diffusion Magnetic Resonance Imaging, Algorithms, Software, Artificial Intelligence, Magnetic Resonance Imaging methods
- Abstract
Fetal magnetic resonance imaging (fetal MRI) is usually performed as a second-level examination following routine ultrasound examination, generally exploiting morphological and diffusion MRI sequences. The objective of this review is to describe the novelties and new applications of fetal MRI, focusing on three main aspects: the new sequences with their applications, the transition from 1.5-T to 3-T magnetic field, and the new applications of artificial intelligence software. This review was carried out by consulting the MEDLINE references (PubMed) and including only peer-reviewed articles written in English. Among the most important novelties in fetal MRI, we find the intravoxel incoherent motion model which allow to discriminate the diffusion from the perfusion component in fetal and placenta tissues. The transition from 1.5-T to 3-T magnetic field allowed for higher quality images, thanks to the higher signal-to-noise ratio with a trade-off of more frequent artifacts. The application of motion-correction software makes it possible to overcome movement artifacts by obtaining higher quality images and to generate three-dimensional images useful in preoperative planning.Relevance statementThis review shows the latest developments offered by fetal MRI focusing on new sequences, transition from 1.5-T to 3-T magnetic field and the emerging role of AI software that are paving the way for new diagnostic strategies.Key points• Fetal magnetic resonance imaging (MRI) is a second-line imaging after ultrasound.• Diffusion-weighted imaging and intravoxel incoherent motion sequences provide quantitative biomarkers on fetal microstructure and perfusion.• 3-T MRI improves the detection of cerebral malformations.• 3-T MRI is useful for both body and nervous system indications.• Automatic MRI motion tracking overcomes fetal movement artifacts and improve fetal imaging., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
35. 3D Culture and Interferon-γ Priming Modulates Characteristics of Mesenchymal Stromal/Stem Cells by Modifying the Expression of Both Intracellular and Exosomal microRNAs.
- Author
-
Bulati M, Gallo A, Zito G, Busà R, Iannolo G, Cuscino N, Castelbuono S, Carcione C, Centi C, Martucci G, Bertani A, Baiamonte MP, Chinnici CM, Conaldi PG, and Miceli V
- Abstract
Mesenchymal stromal/stem cells (MSCs) have emerged as a therapeutic tool in regenerative medicine. Recent studies have shown that exosome (EXO)-derived microRNAs (miRNAs) play a crucial role in mediating MSC functions. Additionally, intracellular miRNAs have been found to regulate MSC therapeutic capacities. However, the molecular mechanisms underlying miRNA-mediated MSC effects are not fully understood. We used 3D culture and IFN-γ to prime/enhance the MSC therapeutic effects in terms of functional miRNAs. After priming, our analysis revealed stable variations in intracellular miRNA among the MSC biological replicates. Conversely, a significant variability of miRNA was observed among EXOs released from biological replicates of the priming treatment. For each priming, we observed distinct miRNA expression profiles between the MSCs and their EXOs. Moreover, in both types of priming, gene ontology (GO) analysis of deregulated miRNAs highlighted their involvement in tissue repair/regeneration pathways. In particular, the 3D culture enhanced angiogenic properties in both MSCs and EXOs, while IFN-γ treatment enriched miRNAs associated with immunomodulatory pathways. These findings suggest that 3D culture and IFN-γ treatment are promising strategies for enhancing the therapeutic potential of MSCs by modulating miRNA expression. Additionally, the identified miRNAs may contribute to understanding the molecular mechanisms underlying the miRNA-mediated therapeutic effects of MSCs.
- Published
- 2023
- Full Text
- View/download PDF
36. Facing the Challenges in the COVID-19 Pandemic Era: From Standard Treatments to the Umbilical Cord-Derived Mesenchymal Stromal Cells as a New Therapeutic Strategy.
- Author
-
Russo E, Corrao S, Di Gaudio F, Alberti G, Caprnda M, Kubatka P, Kruzliak P, Miceli V, Conaldi PG, Borlongan CV, and La Rocca G
- Subjects
- Pregnancy, Female, Humans, Pandemics, SARS-CoV-2 metabolism, COVID-19 Vaccines, Placenta metabolism, Umbilical Cord, Cytokines metabolism, COVID-19 metabolism, Mesenchymal Stem Cells metabolism
- Abstract
Coronavirus disease 2019 (COVID-19), the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which counts more than 650 million cases and more than 6.6 million of deaths worldwide, affects the respiratory system with typical symptoms such as fever, cough, sore throat, acute respiratory distress syndrome (ARDS), and fatigue. Other nonpulmonary manifestations are related with abnormal inflammatory response, the "cytokine storm", that could lead to a multiorgan disease and to death. Evolution of effective vaccines against SARS-CoV-2 provided multiple options to prevent the infection, but the treatment of the severe forms remains difficult to manage. The cytokine storm is usually counteracted with standard medical care and anti-inflammatory drugs, but researchers moved forward their studies on new strategies based on cell therapy approaches. The perinatal tissues, such as placental membranes, amniotic fluid, and umbilical cord derivatives, are enriched in mesenchymal stromal cells (MSCs) that exert a well-known anti-inflammatory role, immune response modulation, and tissue repair. In this review, we focused on umbilical-cord-derived MSCs (UC-MSCs) used in in vitro and in vivo studies in order to evaluate the weakening of the severe symptoms, and on recent clinical trials from different databases, supporting the favorable potential of UC-MSCs as therapeutic strategy.
- Published
- 2023
- Full Text
- View/download PDF
37. Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells: Potential implications for their clinical use.
- Author
-
Miceli V, Zito G, Bulati M, Gallo A, Busà R, Iannolo G, and Conaldi PG
- Abstract
Mesenchymal stromal/stem cells (MSCs) have shown significant therapeutic potential, and have therefore been extensively investigated in preclinical studies of regenerative medicine. However, while MSCs have been shown to be safe as a cellular treatment, they have usually been therapeutically ineffective in human diseases. In fact, in many clinical trials it has been shown that MSCs have moderate or poor efficacy. This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs. Recently, specific priming strategies have been used to improve the therapeutic properties of MSCs. In this review, we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs. We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes. Particularly, while hypoxic priming can be used primarily for the treatment of acute diseases, inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders. The shift in approach from regeneration to inflammation implies, in MSCs, a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways. The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
38. Impact of DWI and ADC values in Ovarian-Adnexal Reporting and Data System (O-RADS) MRI score.
- Author
-
Manganaro L, Ciulla S, Celli V, Ercolani G, Ninkova R, Miceli V, Cozzi A, Rizzo SM, Thomassin-Naggara I, and Catalano C
- Subjects
- Humans, Female, Retrospective Studies, Reproducibility of Results, Sensitivity and Specificity, ROC Curve, Magnetic Resonance Imaging methods, Diffusion Magnetic Resonance Imaging methods
- Abstract
Purpose: Introduce DWI and quantitative ADC evaluation in O-RADS MRI system and observe how diagnostic performance changes. Assess its validity and reproducibility between readers with different experience in female pelvic imaging. Finally, evaluate any correlation between ADC value and histotype in malignant lesions., Materials and Methods: In total, 173 patients with 213 indeterminate adnexal masses (AMs) on ultrasound were subjected to MRI examination, from which 140 patients with 172 AMs were included in the final analysis. Standardised MRI sequences were used, including DWI and DCE sequences. Two readers, blinded to histopathological data, retrospectively classified AMs according to the O-RADS MRI scoring system. A quantitative analysis method was applied by placing a ROI on the ADC maps obtained from single-exponential DWI sequences. AMs considered benign (O-RADS MRI score 2) were excluded from the ADC analysis., Results: Excellent inter-reader agreement was found in the classification of lesions according to the O-RADS MRI score (K = 0.936; 95% CI). Two ROC curves were created to determine the optimal cut-off value for the ADC variable between O-RADS MRI categories 3-4 and 4-5, respectively, 1.411 × 10
-3 mm2 /sec and 0.849 × 10-3 mm2 /sec. Based on these ADC values, 3/45 and 22/62 AMs were upgraded, respectively, to score 4 and 5, while 4/62 AMs were downgraded to score 3. ADC values correlated significantly with the ovarian carcinoma histotype (p value < 0.001)., Conclusion: Our study demonstrates the prognostic potential of DWI and ADC values in the O-RADS MRI classification for better radiological standardisation and characterisation of AMs., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
39. Role of Mesenchymal Stem/Stromal Cells in Modulating Ischemia/Reperfusion Injury: Current State of the Art and Future Perspectives.
- Author
-
Miceli V, Bulati M, Gallo A, Iannolo G, Busà R, Conaldi PG, and Zito G
- Abstract
Ischemia/reperfusion injury (IRI) is a multistep damage that occurs in several tissues when a blood flow interruption is inevitable, such as during organ surgery or transplantation. It is responsible for cell death and tissue dysfunction, thus leading, in the case of transplantation, to organ rejection. IRI takes place during reperfusion, i.e., when blood flow is restored, by activating inflammation and reactive oxygen species (ROS) production, causing mitochondrial damage and apoptosis of parenchymal cells. Unfortunately, none of the therapies currently in use are definitive, prompting the need for new therapeutic approaches. Scientific evidence has proven that mesenchymal stem/stromal cells (MSCs) can reduce inflammation and ROS, prompting this cellular therapy to also be investigated for treatment of IRI. Moreover, it has been shown that MSC therapeutic effects were mediated in part by their secretome, which appears to be involved in immune regulation and tissue repair. For these reasons, mediated MSC paracrine function might be key for injury amelioration upon IRI damage. In this review, we highlight the scientific literature on the potential beneficial use of MSCs and their products for improving IRI outcomes in different tissues/organs, focusing in particular on the paracrine effects mediated by MSCs, and on the molecular mechanisms behind these effects.
- Published
- 2023
- Full Text
- View/download PDF
40. Stem cell therapy in the treatment of organic and dysfunctional endometrial pathology.
- Author
-
Cittadini E, Brucculeri AM, Quartararo F, Vaglica R, Miceli V, and Conaldi PG
- Subjects
- Pregnancy, Female, Humans, Stem Cell Transplantation methods, Adipose Tissue metabolism, Stromal Cells metabolism, Tissue Adhesions metabolism, Endometrium metabolism, Uterine Diseases metabolism
- Abstract
Background: Intrauterine adhesions caused by postpartum curettage, spontaneous abortions, interrupted pregnancies, endometrial ablations, infections and inflammations, can lead to a loss of endometrial function, with consequent hypomenorrhea and infertility in women of reproductive age. In a non-negligible percentage of cases, the available surgical methods and hormone therapy, with sequential administration of estrogen and progesterone, are ineffective. In fact, severe damage to the basal layer of the endometrium causes the loss of endometrial cell precursors and leads to the failure of regeneration of the functional layer to which the endometrium is cyclically exposed. Today, many researchers are evaluating the use of stem cells of different origins as a potential therapy to restore endometrial function., Methods: Our interest has been focused on adipose-derived stromal/stem cells (ADSCs) obtained by collecting subcutaneous adipose tissue and subsequently treating it with the MilliGraft
® method. This procedure produces a cell suspension, the stromal vascular fraction (SVF), which includes ADSCs and soluble factors such as proteins and extracellular vesicles (exosomes). The SVF thus obtained was characterized in its cellular composition and its functional factors. Our clinical protocol for the future use of adipose tissue in endometrial regeneration in its different phases is presented., Results: The data obtained, even though they still require further support and implementation, show the regenerative properties of SVF obtained from adipose tissue using a mechanical method., Conclusions: These findings can contribute to the development of cell therapies using stem cells of different derivations which are increasingly being utilized in the treatment of endometrial lesions from adherent or dysfunctional pathologies.- Published
- 2022
- Full Text
- View/download PDF
41. Long-Term Effectiveness of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine on B Cell Compartment: Efficient Recall of SARS-CoV-2-Specific Memory B Cells.
- Author
-
Busà R, Miele M, Sorrentino MC, Amico G, Timoneri F, Miceli V, Di Bella M, Russelli G, Gallo A, Zito G, Iannolo G, Conaldi PG, and Bulati M
- Subjects
- Humans, SARS-CoV-2, BNT162 Vaccine, RNA, Messenger genetics, Immunoglobulin G, Antibodies, Viral, Memory B Cells, COVID-19 prevention & control
- Abstract
At present, there is a lack of clinical evidence about the impact and long-term durability of the immune response induced by the third dose of mRNA vaccines. In this study, we followed up the B cell compartment behavior in a cohort of immunocompetent individuals three and six months after the third dose of vaccine. During this period, some subjects contracted the virus. In uninfected vaccinated subjects, we did not report any changes in serum spike-specific IgG levels, with a significant reduction in IgA. Instead, subjects recovered from natural infection showed a significant increase in both specific IgG and IgA. Moreover, we showed a time-related decrease in IgG neutralizing potential to all SARS-CoV-2 variants of concern (VOC) in uninfected compared to recovered subjects, who displayed an increased neutralizing ability, particularly against the omicron variant. Finally, we underlined the presence of a pool of SARS-CoV-2-specific B cells in both groups that are prone to respond to restimulation, as demonstrated by their ability to differentiate into plasma cells and to produce anti-SARS-CoV-2-specific immunoglobulins. These data lead us to assert the long-term effectiveness of the BNT162b2 vaccine in contrasting the severe form of the pathology and prevent COVID-19-associated hospitalization.
- Published
- 2022
- Full Text
- View/download PDF
42. Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications.
- Author
-
Alberti G, Russo E, Corrao S, Anzalone R, Kruzliak P, Miceli V, Conaldi PG, Di Gaudio F, and La Rocca G
- Abstract
Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of parental cells were maintained by isolated EV populations. This review analyzes the recent development in the field of cell-free therapies, focusing on several adult tissues as a source of MSC-derived EVs and the available clinical data from in vivo models.
- Published
- 2022
- Full Text
- View/download PDF
43. Hepatocellular carcinoma, hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches.
- Author
-
Badami E, Busà R, Douradinha B, Russelli G, Miceli V, Gallo A, Zito G, Conaldi PG, and Iannolo G
- Subjects
- Hepacivirus genetics, Humans, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular therapy, Hepatitis C complications, Hepatitis C genetics, Hepatitis C pathology, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic pathology, Liver Neoplasms genetics, Liver Neoplasms therapy, MicroRNAs genetics, MicroRNAs therapeutic use
- Abstract
Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%-20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
44. Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components.
- Author
-
Busà R, Sorrentino MC, Russelli G, Amico G, Miceli V, Miele M, Di Bella M, Timoneri F, Gallo A, Zito G, Di Carlo D, Conaldi PG, and Bulati M
- Subjects
- BNT162 Vaccine, COVID-19 Vaccines, Humans, Immunity, Cellular, RNA, Messenger genetics, T-Lymphocytes, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, SARS-CoV-2
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is modifying human activity all over the world with significant health and economic burden. The advent of the SARS-CoV-2 pandemic prompted the scientific community to learn the virus dynamics concerning transmissibility, epidemiology, and usefulness of vaccines in fighting emerging health hazards. Pieces of evidence suggest that the first and second doses of mRNA vaccines induce a significant antibody response in vaccinated subjects or patients who recovered from SARS-CoV-2 infection, demonstrating the importance of the previously formed memory. The aim of this work has been to investigate the effects of BNT162b2 Pfizer-BioNTech mRNA-based vaccine booster dose in a cohort of 11 uninfected immunocompetent (ICs), evaluating the humoral and cellular responses, with more carefulness on memory B and T cells. Our findings underscore the potential benefit of the third dose of mRNA vaccine on the lifespan of memory B and T cells, suggesting that booster doses could increase protection against SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Busà, Sorrentino, Russelli, Amico, Miceli, Miele, Di Bella, Timoneri, Gallo, Zito, Di Carlo, Conaldi and Bulati.)
- Published
- 2022
- Full Text
- View/download PDF
45. In Vitro Evaluation of Nanoerythrosome Cytotoxicity and Uptake in Pancreatic Endothelial Cells: Implications for β-Cell Imaging Applications.
- Author
-
Miceli V, Fornasier M, Bulati M, Amico G, Conaldi PG, Casu A, and Murgia S
- Subjects
- Animals, Biological Transport, Cell Line, Insulin metabolism, Mice, Rats, Endothelial Cells metabolism, Insulin-Secreting Cells metabolism
- Abstract
Biomolecule-targeted imaging represents one of the most difficult challenges in medicine. Nanoerythrosomes (NERs) are nanovesicles obtained after lysis of red blood cells, and they are promising tools for drug delivery and imaging. In this work, a formulation based on NERs functionalized with 7-amino-3-methylcoumarin via cross-linking was tested on rat INS-1E and mouse MIN6 β-cells and endothelial MSI cell lines. First, the morphology, size, ζ-potentials, and spectroscopic properties of the aggregates were investigated, highlighting that the functionalization did not significantly affect the nanoparticles' physicochemical features. In vitro , the nanoparticles did not significantly affect the proliferation and function of INS-1E and MIN6 β-cells at different concentrations. Only at the highest concentration tested on the MSI cell line, the formulation inhibited proliferation. Furthermore, NER aggregates were not internalized in both INS-1E and MIN6 cell lines, while a diffuse fluorescence was noticed in the cytosol of the MSI cell line at the highest concentrations. These findings proved that NER formulations might represent a new nanotool for β-cell imaging as a part of a strategy aimed to prevent any intracellular accumulation, thus reducing/avoiding side effects.
- Published
- 2022
- Full Text
- View/download PDF
46. Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation.
- Author
-
Miceli V and Bertani A
- Subjects
- Humans, Lung, Perfusion, Lung Transplantation, Mesenchymal Stem Cells, Reperfusion Injury therapy
- Abstract
Lung transplantation (LTx) has become the gold standard treatment for end-stage respiratory failure. Recently, extended lung donor criteria have been applied to decrease the mortality rate of patients on the waiting list. Moreover, ex vivo lung perfusion (EVLP) has been used to improve the number/quality of previously unacceptable lungs. Despite the above-mentioned progress, the morbidity/mortality of LTx remains high compared to other solid organ transplants. Lungs are particularly susceptible to ischemia-reperfusion injury, which can lead to graft dysfunction. Therefore, the success of LTx is related to the quality/function of the graft, and EVLP represents an opportunity to protect/regenerate the lungs before transplantation. Increasing evidence supports the use of mesenchymal stromal/stem cells (MSCs) as a therapeutic strategy to improve EVLP. The therapeutic properties of MSC are partially mediated by secreted factors. Hence, the strategy of lung perfusion with MSCs and/or their products pave the way for a new innovative approach that further increases the potential for the use of EVLP. This article provides an overview of experimental, preclinical and clinical studies supporting the application of MSCs to improve EVLP, the ultimate goal being efficient organ reconditioning in order to expand the donor lung pool and to improve transplant outcomes.
- Published
- 2022
- Full Text
- View/download PDF
47. Human Amnion-Derived Mesenchymal Stromal/Stem Cells Pre-Conditioning Inhibits Inflammation and Apoptosis of Immune and Parenchymal Cells in an In Vitro Model of Liver Ischemia/Reperfusion.
- Author
-
Zito G, Miceli V, Carcione C, Busà R, Bulati M, Gallo A, Iannolo G, Pagano D, and Conaldi PG
- Subjects
- Amnion, Apoptosis, Humans, Immunologic Factors pharmacology, Inflammation metabolism, Ischemia metabolism, Reperfusion, Liver Diseases metabolism, Mesenchymal Stem Cells metabolism
- Abstract
Ischemia/reperfusion injury (IRI) represents one of the leading causes of primary non-function acute liver transplantation failure. IRI, generated by an interruption of organ blood flow and the subsequent restoration upon transplant, i.e., reperfusion, generates the activation of an inflammatory cascade from the resident Kupffer cells, leading first to neutrophils recruitment and second to apoptosis of the parenchyma. Recently, human mesenchymal stromal/stem cells (hMSCs) and derivatives have been implemented for reducing the damage induced by IRI. Interestingly, sparse data in the literature have described the use of human amnion-derived MSCs (hAMSCs) and, more importantly, no evidence regarding hMSCs priming on liver IRI have been described yet. Thus, our study focused on the definition of an in vitro model of liver IRI to test the effect of primed hAMSCs to reduce IRI damage on immune and hepatic cells. We found that the IFNγ pre-treatment and 3D culture of hAMSCs strongly reduced inflammation induced by M1-differentiated macrophages. Furthermore, primed hAMSCs significantly inhibited parenchymal apoptosis at early timepoints of reperfusion by blocking the activation of caspase 3/7. All together, these data demonstrate that hAMSCs priming significantly overcomes IRI effects in vitro by engaging the possibility of defining the molecular pathways involved in this process.
- Published
- 2022
- Full Text
- View/download PDF
48. Changes in the Transcriptome Profiles of Human Amnion-Derived Mesenchymal Stromal/Stem Cells Induced by Three-Dimensional Culture: A Potential Priming Strategy to Improve Their Properties.
- Author
-
Gallo A, Cuscino N, Contino F, Bulati M, Pampalone M, Amico G, Zito G, Carcione C, Centi C, Bertani A, Conaldi PG, and Miceli V
- Subjects
- Biomarkers, Cell Culture Techniques, Cell Differentiation, Cell Separation, Cells, Cultured, Computational Biology methods, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, Humans, Immunophenotyping, Mesenchymal Stem Cells cytology, Molecular Sequence Annotation, Regenerative Medicine, Amnion cytology, Mesenchymal Stem Cells metabolism, Transcriptome
- Abstract
Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.
- Published
- 2022
- Full Text
- View/download PDF
49. Antihypertensive Peptides from Ultrafiltration and Fermentation of the Ricotta Cheese Exhausted Whey: Design and Characterization of a Functional Ricotta Cheese.
- Author
-
Pontonio E, Montemurro M, De Gennaro GV, Miceli V, and Rizzello CG
- Abstract
Aiming at valorizing the ricotta cheese exhausted whey (RCEW), one of the most abundant by-products from the dairy industry, a biotechnological protocol to obtain bioactive peptides with angiotensin-I-converting enzyme (ACE)-inhibitory activity was set up. The approach was based on the combination of membrane filtration and fermentation. A Lactobacillus helveticus strain selected to be used as starter for the fermentation of the ultrafiltration protein-rich retentate (R-UF) obtained from RCEW. The fermented R-UF was characterized by a high anti-ACE activity. Peptides responsible for the bioactivity were purified and identified through nano-LC-ESI-MS/MS. The sequences identified in the purified active fractions of the fermented R-UF showed partial or complete overlapping with previously reported κ-casein antihypertensive fragments. The fermented R-UF was spray-dried and used to enrich ricotta cheese at different fortification level (1 and 5% w / w ). An integrated approach including the assessment of the microbiological, chemical, functional, textural, and sensory properties was used to characterize the fortified products. A significantly higher anti-ACE activity was found in the ricotta cheese fortified with fermented R-UF as compared to the control and to the samples obtained with the unfermented R-UF fraction at the same levels of fortification. In particular, a 100 g portion of the ricotta cheese produced at 5% fortification level contained circa 30 mg of bioactive peptides. The fortification led to a moderate acidification, increased hardness and chewiness, and decreased the milk odor and taste of the ricotta cheese as compared to the control, while flavor persistence and sapidity improved.
- Published
- 2021
- Full Text
- View/download PDF
50. Amnion-Derived Mesenchymal Stromal/Stem Cell Paracrine Signals Potentiate Human Liver Organoid Differentiation: Translational Implications for Liver Regeneration.
- Author
-
Lo Nigro A, Gallo A, Bulati M, Vitale G, Paini DS, Pampalone M, Galvagno D, Conaldi PG, and Miceli V
- Abstract
The prevalence of end-stage liver diseases has reached very high levels globally. The election treatment for affected patients is orthotopic liver transplantation, which is a very complex procedure, and due to the limited number of suitable organ donors, considerable research is being done on alternative therapeutic options. For instance, the use of cell therapy, such as the transplantation of hepatocytes to promote liver repair/regeneration, has been explored, but standardized protocols to produce suitable human hepatocytes are still limited. On the other hand, liver progenitor and multipotent stem cells offer potential cell sources that could be used clinically. Different studies have reported regarding the therapeutic effects of transplanted mesenchymal stromal/stem cells (MSCs) on end-stage liver diseases. Moreover, it has been shown that delivery of MSC-derived conditioned medium (MSC-CM) can reduce cell death and enhance liver proliferation in fulminant hepatic failure. Therefore, it is believed that MSC-CM contains many factors that probably support liver regeneration. In our work, we used an in vitro model of human liver organoids to study if the paracrine components secreted by human amnion-derived MSCs (hAMSCs) affected liver stem/progenitor cell differentiation. In particular, we differentiated liver organoids derived from bipotent EpCAM
+ human liver cells and tested the effects of hAMSC secretome, derived from both two-dimensional (2D) and three-dimensional (3D) hAMSC cultures, on that model. Our analysis showed that conditioned medium (CM) produced by 3D hAMSCs was able to induce an over-expression of mature hepatocyte markers, such as ALB, NTCP, and CYP3A4, compared with both 2D hAMSC cultures and the conventional differentiation medium (DM). These data were confirmed by the over-production of ALB protein and over-activity of CYP3A4 observed in organoids grown in 3D hAMSC-CM. Liver repair dysfunction plays a role in the development of liver diseases, and effective repair likely requires the normal functioning of liver stem/progenitor cells. Herein, we showed that hAMSC-CM produced mainly by 3D cultures had the potential to increase hepatic stem/progenitor cell differentiation, demonstrating that soluble factors secreted by those cells are potentially responsible for the reaction. This work shows a potential approach to improve liver repair/regeneration also in a transplantation setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lo Nigro, Gallo, Bulati, Vitale, Paini, Pampalone, Galvagno, Conaldi and Miceli.)- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.