Biomaterial containing extracellular matrix for pancreatic islet microencapsulation and reversion of Diabetes induced in animals.

• Grant number: 23/09475-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Henrique Capistrano de Melo
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/05311-2 - Regenerative medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes), AP.TEM

Abstract

Diabetes mellitus (DM) is a global Health emergency, being one of the main causes of death in the World. Type 1 diabetes (T1D), which represents around 10% of the cases, is characterized by autoimmune destruction of the insulin-producing beta cells of the pancreas, leading to absolute exogenous insulin requirement therapy for patient survival. Whole organ pâncreas transplantation and pancreatic islet transplantation constitute promising alternatives, however, both of them are limited by the scarcity of organ donors and, also, by the serious side effects of the immunossupressive therapy, which is required in the case of allotransplantation. We have been isolating porcine pancreatic islets, which may be cultured in monolayers (2D cultures) and as tridimensional spheroids (3D cultures). Aiming at optimizing the viability and functionality of porcine pancreatic islets and spheroids, we propose to add elements of the extracelular matrix (ECM) to the biomaterial used for microencapsulation, since the microenvironment is crucial for insulin-producing cells. This projects aims at developing microcapsules using a mixture of a biomaterial and porcine MEC generated by pancreas descellularization. The objective is to generate MEC-containing microcapsules to immunoisolate and protect the porcine islets and spheroids and evaluate their efficacy in cell transplantation in animals rendered diabetic by streptozotocin injection, which specifically destroys insulin-producing beta cells, in the absence of immunossupressive treatment. This study should contribute to advances in T1D treatment and improvement of the patients quality of life.