Stem Cell Based Models in Congenital Hyperinsulinism - Perspective on Practicalities and Possibilities.

Väinö Lithovius,Timo Otonkoski

doi:10.3389/fendo.2022.837450

Abstract

Congenital hyperinsulinism (CHI) is a severe inherited neonatal disorder characterized by inappropriate insulin secretion caused by genetic defects of the pancreatic beta cells. Several open questions remain in CHI research, such as the optimal treatment for the most common type of CHI, caused by mutations in the genes encoding ATP-sensitive potassium channels, and the molecular mechanisms of newly identified CHI genes. Answering these questions requires robust preclinical models, particularly since primary patient material is extremely scarce and accurate animal models are not available. In this short review, we explain why pluripotent stem cell derived islets present an attractive solution to these issues and outline the current progress in stem-cell based modeling of CHI. Stem cell derived islets enable the study of molecular mechanisms of CHI and the discovery of novel antihypoglycemic drugs, while also providing a valuable model to study the biology of variable functional states of beta cells.

Highlights

Congenital hyperinsulinism (CHI), characterized by inappropriate insulin secretion from the pancreatic beta cells, is the most common cause of persistent childhood hypoglycemia
This review focuses on the use of Pluripotent stem cells (PSCs)-derived pancreatic islets (SC-islets) for preclinical study of congenital hyperinsulinism
Generating isogenic controls with genome editing of the PSCs can be considered as the ideal approach for the effective modeling of a genetic disease such as CHI

Summary

Introduction

Congenital hyperinsulinism (CHI), characterized by inappropriate insulin secretion from the pancreatic beta cells, is the most common cause of persistent childhood hypoglycemia. Generating isogenic controls with genome editing of the PSCs can be considered as the ideal approach for the effective modeling of a genetic disease such as CHI. Regardless of the specifics, genome editing technology has matured to a state where generating disease relevant stem cell lines for further differentiation is practical.

Results

Conclusion