Generation and characterization of insulin-producing cells (IPCs) from induced pluripotent stem cells (iPSCs).

• Grant number: 25/00685-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Lucas Pilenso Silveira
• 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 metabolic syndrome with high global prevalence, considered one of the greatest public health emergencies of the 21st century. It is among the top 10 leading causes of death worldwide, and its increasing incidence is linked to modern lifestyles, such as poor diets, sedentary behavior, and obesity. DM is responsible for more than 80% of premature deaths globally, along with cardiovascular diseases, cancer, and respiratory diseases. In addition, it leads to various severe complications, such as heart attacks, strokes, kidney failure, amputations, blindness, and skin ulcers.Type 1 Diabetes (T1D) is a form of DM that represents 5 to 10% of cases. In this type, there is autoimmune destruction of the ¿ cells of the islets of Langerhans in the pancreas, which are responsible for insulin production, resulting in the loss of the body's ability to produce insulin endogenously. As a consequence, patients become dependent on exogenous insulin (insulin therapy) for glycemic control. Although insulin therapy is the most common treatment and is effective, it does not prevent all the complications of the disease, nor is it fully effective in more severe cases. Alternatives include pancreas or islet transplantation, the latter still being an experimental treatment, but both present challenges such as the shortage of suitable donor organs and the complications caused by the immunosuppressive therapy required to prevent graft rejection.Given this scenario, there is a need to develop new therapeutic approaches for glycemic control. Current research focuses on the development of insulin-producing cells (IPCs) that could be used in transplants for patients with T1D. In this context, stem cells have been shown to be a promising alternative, since they display self-renewal capability and can differentiate into various cell types, including IPCs, after an appropriate differentiation process.Among the types of stem cells, induced pluripotent stem cells (iPSCs) stand out for their ability to generate pancreatic islets with high efficiency and stability. The improvement of differentiation protocols for these cells, along with the ease of obtaining the initial cells, render iPSCs as an attractive option for IPCs production, being a promising field for future treatments.The goal of this project is to contribute to the characterization of the steps involved in generating insulin-producing cells from iPSCs, with a particular focus on the characterization of the endocrine precursors of these cells. The development of these cells could offer a viable alternative for patients with Type 1 Diabetes, providing an innovative therapy to replace the endogenous insulin lost due to the destruction of pancreatic ¿ cells.