Immune Regulatory Properties of Allogeneic Adipose-Derived Mesenchymal Stem Cells in the Treatment of Experimental Autoimmune Diabetes

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dc.contributor.authorBassi, Enio J.
dc.contributor.authorMoraes-Vieira, Pedro M. M.
dc.contributor.authorMoreira-Sa, Carla S. R.
dc.contributor.authorAlmeida, Danilo C. [UNIFESP]
dc.contributor.authorVieira, Leonardo M.
dc.contributor.authorCunha, Claudia S.
dc.contributor.authorHiyane, Meire Ioshie [UNIFESP]
dc.contributor.authorBasso, Alexandre S. [UNIFESP]
dc.contributor.authorPacheco-Silva, Alvaro [UNIFESP]
dc.contributor.authorCâmara, Niels Olsen Saraiva [UNIFESP]
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:27:46Z
dc.date.available2016-01-24T14:27:46Z
dc.date.issued2012-10-01
dc.description.abstractAdipose-derived mesenchymal stem cells (ADMSCs) display immunosuppressive properties, suggesting a promising therapeutic application in several autoimmune diseases, but their role in type 1 diabetes (T1D) remains largely unexplored. the aim of this study was to investigate the immune regulatory properties of allogeneic ADMSC therapy in T cell-mediated autoimmune diabetes in NOD mice. ADMSC treatment reversed the hyperglycemia of early-onset diabetes in 78% of diabetic NOD mice, and this effect was associated with higher serum insulin, amylin, and glucagon-like peptide 1 levels compared with untreated controls. This improved outcome was associated with downregulation of the CD4(+) Th1-biased immune response and expansion of regulatory T cells (Tregs) in the pancreatic lymph nodes. Within the pancreas, inflammatory cell infiltration and interferon-gamma levels were reduced, while insulin, pancreatic duodenal homeobox-1, and active transforming growth factor-beta 1 expression were increased. in vitro, ADMSCs induced the expansion/proliferation of Tregs in a cell contact-dependent manner mediated by programmed death ligand 1. in summary, ADMSC therapy efficiently ameliorates autoimmune diabetes pathogenesis in diabetic NOD mice by attenuating the Th1 immune response concomitant with the expansion/proliferation of Tregs, thereby contributing to the maintenance of functional beta-cells. Thus, this study may provide a new perspective for the development of ADMSC-based cellular therapies for T1D. Diabetes 61:2534-2545, 2012en
dc.description.affiliationUniv São Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipState of São Paulo Foundation
dc.description.sponsorshipBrazilian Council of Scientific and Technologic Development
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipNational Institute of Science and Technology on Complex Fluids
dc.description.sponsorshipIDState of São Paulo Foundation: 07/07139-3
dc.description.sponsorshipIDState of São Paulo Foundation: 09/51649-1
dc.description.sponsorshipIDState of São Paulo Foundation: 2010/52180-4
dc.description.sponsorshipIDState of São Paulo Foundation: 2010/12295-7
dc.description.sponsorshipIDState of São Paulo Foundation: 2010/16213-5
dc.description.sponsorshipIDBrazilian Council of Scientific and Technologic Development: 501278/2010-9
dc.description.sponsorshipIDBrazilian Council of Scientific and Technologic Development: 500842/2010-8
dc.description.sponsorshipIDBrazilian Council of Scientific and Technologic Development: 470456/2010-8
dc.description.sponsorshipIDCNPq: 573815/2008-9
dc.format.extent2534-2545
dc.identifierhttp://dx.doi.org/10.2337/db11-0844
dc.identifier.citationDiabetes. Alexandria: Amer Diabetes Assoc, v. 61, n. 10, p. 2534-2545, 2012.
dc.identifier.doi10.2337/db11-0844
dc.identifier.issn0012-1797
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35331
dc.identifier.wosWOS:000309304600018
dc.language.isoeng
dc.publisherAmer Diabetes Assoc
dc.relation.ispartofDiabetes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleImmune Regulatory Properties of Allogeneic Adipose-Derived Mesenchymal Stem Cells in the Treatment of Experimental Autoimmune Diabetesen
dc.typeinfo:eu-repo/semantics/article
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