Role of pancreatic mesenchymal stromal cells in the pathogenesis of autoimune diabetes

• Grant number: 12/50768-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2014
• End date: June 30, 2016
• Field of knowledge: Biological Sciences - Immunology
• Agreement: CNPq - First Projects Program
• Principal Investigator: Kelen Cristina Ribeiro Malmegrim de Farias
• Grantee: Kelen Cristina Ribeiro Malmegrim de Farias
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Multipotent mesenchymal stromal cells are found in the stroma of all adult tissue and probably located at the perivascular niche. Due to their location, regenerative, immunossupressive and immunoregulatory properties, it has been suggested that these cells work like in vivo stromal sentinels inhibiting potential inflammatory tissue-destructive responses and regulating tissue regeneration. In the last years, populations of pancreatic mesenchymal stromal cells (pMSCs) were reported in endocrine and exocrine pancreatic tissue cultures. Nevertheless, there are no conclusive results regarding their in vivo location, true origin, and role in the pancreatic tissue. Thus, the hypothesis of this work is that pMSCs share biological and immunoregulatory characteristics with other stromal populations, and also undergo continuous modulation by the pancreatic microenvironment during ali phases of experimental autoimmune diabetes development and progression. The objective of this project is to study the role of pancreatic mesenchymal stromal cells in the pathogenesis of experimental autoimmune diabetes. For that, we have established specific goals: 1, To isolate and characterize pMSCs from BALB/c mice; 2, To characterize freshly isolated pMSCs from BALB/c mice by flow cytometry sorting; 3, To determine the mechanisms involved in the immunossupressive and immunoregulatory properties of pMSCs; 4, To investigate the effects of hyperglycemia in the immunossupressive and immunoregulatory properties of pMCSs; 5, To determine the involvement of pMSCs during the development and pathogenesis of experimental autoimmune diabetes; 6, To determine the in situ location of pMSCs in control BALB/c mice and in all phases of experimental autoimmune diabetes development in NOD mice. (AU)