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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Bassi, Enio J. [1] ; Moraes-Vieira, Pedro M. M. [1] ; Moreira-Sa, Carla S. R. [1] ; Almeida, Danilo C. [2] ; Vieira, Leonardo M. [1] ; Cunha, Claudia S. [1] ; Hiyane, Meire I. [1] ; Basso, Alexandre S. [3] ; Pacheco-Silva, Alvaro [2] ; Camara, Niels O. S. [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Div Nephrol, Dept Med, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Diabetes; v. 61, n. 10, p. 2534-2545, OCT 2012.
Web of Science Citations: 75
Abstract

Adipose-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, 2012 (AU)

FAPESP's process: 10/12295-7 - MicroRNA profile during the repair of cisplatin-induced renal tissue and cells injury by therapy with mesenchymal stem cells derived from adipose tissue.
Grantee:Danilo Candido de Almeida
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
Grantee:Niels Olsen Saraiva Câmara
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/16213-5 - Global expression profile of microRNAs in tissue and cell repair induced by adipose tissue-derived mesenchymal stem cells.
Grantee:Niels Olsen Saraiva Câmara
Support type: Regular Research Grants