Influence of peptide growth/differentiation factors in the process of murine embryonic stem cells (mESCs) differentiation into insulin-producing cells (IPCs)

• Grant number: 19/22267-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2020
• Effective date (End): January 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Mari Cleide Sogayar
• Grantee: Camila Harumi Kimura
• Home Institution: Faculdade de Medicina (FM). 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

Type 1 diabetes mellitus (DM1) is characterized by autoimmune destruction of insulin-producing pancreatic ² cells, a hormone which has a regulating role of carbohydrate metabolism and blood glucose levels (glycemia). The treatment of DM1 is mainly based on insulin administration, which not always prevent the deleterious effects of hyperglycemia (kidney, eye, neuronal and cardiovascular injuries). Therefore, the search for new therapeutic interventions to maintain normoglycemia in patients with DM1 is a growing need. Pancreas transplantation allows restoration of normoglycemia, but constitutes a large, invasive and high-risk surgery procedure for the patient, in addition to requiring the use of immunosuppression, since it is an allograft. On the other hand, pancreatic islet transplantation, which was introduced in Brazil by our research group, is much simpler and less invasive than pancreas transplantation, being a promising therapeutic alternative for DM1, although it is limited by the availability of organ (pancreas) donors and by the fact that it also requires patient immunosuppression. To avoid the need for immunosuppression and to face the problem of low availability of pancreas from organ donors for the generation of pancreatic islets, our group proposed the islet encapsulation/immunoisolation strategy and the generation of insulin-producing cells (IPCs) from murine embryonic stem cells (mESCs), respectively. In this project, we aim to induce mESCs differentiation into IPCs in the absence and presence of recombinant human peptide growth/differentiation factors produced in our laboratory (rhPDGF-BB, rhBMP7, rhVEGF), followed by an analysis of the functionality of these IPCs by in vitro insulin production assays upon glucose stimulation and, in the future, by reversal of diabetes-induced in animal models.