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Immunoprotection of Pancreatic Islets Microencapsulated in Cytoactive Polymers: Analysis of Proteins Involved in Apoptosis

Grant number: 10/18308-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2010
Effective date (End): November 30, 2011
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Thiago Rennó dos Mares Guia
Grantee:Talita Cristina de Oliveira
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic disease caused by the autoimmune destruction of pancreatic beta cells, characterized by insulin deficiency, hyperglycemia and consequent impairment of the metabolism of carbohydrates, lipids and proteins. The long-term complications, associated with high morbidity and mortality, include the development of vasculopathy and neuropathy. The current treatments for T1DM are insulin therapy and, when it is necessary, pancreas transplant. The transplantation of pancreatic islets, still experimental, emerges as a promising alternative to existing treatments and has been developed in various research centers worldwide, including ours (NUCEL - Cell and Molecular Therapy Center, USP). However, patients who receive pancreas or islet transplants are subjected to a immunosuppressive regimen for the rest of life, resulting in a high financial cost and often causing significant side effects. The microencapsulation of pancreatic islets in biocompatible polymers enables the transplantation of islets without immunosuppression. The immunomodulation achieved with this method results from the permeability of the capsule membrane, which prevents the entry of cells from the immune system and antibodies, but ensures, at the same time, the diffusion of metabolites, nutrients, electrolytes, glucose and oxygen and the output of insulin secreted by islets. The Biodritin is a biocompatible material, composed of alginate and chondroitin sulfate, used in the microencapsulation of pancreatic islets (MARES-GUIA et al., 2003). Our group has developed new biomaterials based on Biodritin containing cytoprotective and cytoactive molecules that confer advantages on the microencapsulated cells or tissues. Preliminary studies with these new formulations showed an increase in the functionality and viability of islets microencapsulated with these substances. This project aims to analyze the expression and activity of proteins associated with apoptosis in murine pancreatic islets microencapsulated with different formulations of biomaterials and maintained in culture under normoxic and hipoxic atmospheres of normoxia and hypoxia, through the analysis by Western blotting and caspase activity assays.

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