title: Restoration of t cell substes of patients with type 1 diabetes mellitus by microencapsulated human umbilical cord Wharton jelly-derived mesenchymal stem cells: An in vitro study.
abstract: Human umbilical cord Wharton jelly-derived mesenchymal stem cells (hUCMS) might apply to treating chronic autoimmune disorders, as already shown for Sjögren's syndrome, including type 1 diabetes mellitus (T1D). Since naked hUCMS grafts encountered restraints, we enveloped hUCMS, within immunoisolatory microcapsules (CpS-hUCMS), made of our endotoxin-free, clinical grade alginate. We then examined the vitro effects of interferon (IFN)-γ-pretreated CpS-hUCMS on Th17 and Treg of T1D patients (n=15) and healthy controls (n=10). Peripheral blood mononuclear cells (PBMCs) were co-cultured with PBMC/CpS-hUCMS: lymphocyte proliferation was assessed by carboxyfluorescein succinimidyl esther (CFSE) dilution assay, and phenotypic analysis of regulatory and effector Tc was also performed. Cytokine expression was performed by bead array and qPCR on IFN-γ-pretreated hUCMS before PBMCs co-culture. CpS-hUCMS restored a correct Treg/Th17 ratio, relevant to the T1D disease process. In summary, we have preliminarily developed a new biohybrid system, associated with immunoregulatory properties, that is ready for in vivo application.
authors.affiliation: Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: pia.montanucci@unipg.it.
authors.forename: Pia
authors.initials: P
authors.lastname: Montanucci
authors.affiliation: Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: alessia.alunno@libero.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Alunno
authors.affiliation: Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: gius.basta@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basta
authors.affiliation: Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: o.bistoni@libero.it.
authors.forename: Onelia
authors.initials: O
authors.lastname: Bistoni
authors.affiliation: Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: teresa_pescara@virgilio.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pescara
authors.affiliation: Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: s.cater@alice.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Caterbi
authors.affiliation: Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: ilaria.pen@libero.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pennoni
authors.affiliation: Department of Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: vittorio.bini@unipg.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.affiliation: Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: roberto.gerli@unipg.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gerli
authors.affiliation: Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: riccardo.calafiore@unipg.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calafiore
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D002214:Capsules; D016022:Case-Control Studies; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D059951:HLA-G Antigens / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014470:Umbilical Cord; D059631:Wharton Jelly / Q000166:cytology; D000098546:Interleukin-21
chemical_list: D000998:Antiviral Agents; D002214:Capsules; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D059951:HLA-G Antigens; C576710:IDO1 protein, human; C508609:IL10 protein, human; C508717:IL17A protein, human; C508594:IL2 protein, human; C508600:IL6 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; C439524:TNF protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D007041:Hypoxanthine Phosphoribosyltransferase; D000098546:Interleukin-21
keywords: Adult mesenchymal stem cell; HLAG-5; Immunomodulation; Microencapsulation; Proliferation inhibition; Type 1 diabetes mellitus