Chapter 35 - Generation of pancreatic islets from stem cells

Abstract

Diabetes mellitus caused by the destruction of β-cell through autoimmune-mediate attack has become the most serious, chronic, and expensive disease. The related glucose homeostasis disruption leads to acute complications or death if left untreated. As the only available treatment for diabetes consist of exogenous insulin supply and while islet transplantation temporarily confers normoglycemia to patients, the lack of a renewable source of insulin-producing β-cells hampers the use of this treatment option. Although significant hurdles remain, in the last decade, tremendous progress has been made in generating insulin-producing cells from both mouse and human pluripotent stem cells. Following the principles that guide pancreas embryonic development is a common aspect in all differentiation protocols with considerable success in generating β-like cells in vitro. Greatest outcome of the refined protocols became apparent in the first clinical trial announced by the ViaCyte, Inc. in October 2014 and recently in Europe by the Center for Beta Cell Therapy in Diabetes (Brussels) in January 2019, based on the implantation of pancreatic progenitors that would further mature into functional insulin-producing cells inside the patient’s body. In this chapter, we will update and discuss the state-of-the-art in β-cell–replacement therapies based on the differentiation of pluripotent stem cells into glucose-response and insulin-producing cells of potential use in the treatment of type I diabetes.