Amplifying human beta cell differentiation using small molecules – BromoBeta

Type 1 and type 2 diabetes both result in insufficient functional pancreatic ß-cell mass. Replenishing the pancreas with new functioning ß-cells represents an innovative strategy for the treatment of diabetes. We recently discovered that a new class of inhibitors could modulate pancreatic endocrine cell development in rodent models, but also in human models of induced Pluripotent Stem Cells (iPSC)-derived ß-cells.
In this consortium, our objective is to determine how these new inhibitors modulate the pancreatic ß-cell mass.
Our strategy is built on 3 teams: Two academic INSERM teams directed by Dr Scharfmann (PI, Paris) and Collombat (Co-PI, Nice) who will mainly concentrate on these new inhibitors in models of rodent ß-cell differentiation and regeneration; one industrial Danish team (Dr Honoré) from Novo Nordisk A/S that will aim at translating data from rodent to human models of iPSC differentiation into ß-cells.
Our project is decomposed into three aims:
Aim 1 (PI: Raphael Scharfmann): to further understand, using rodent in vitro models, how these new inhibitors modulate pancreatic endocrine cell development:
Aim 2 (PI: Christian Honore; Co-PI: Raphael Scharfmann): To translate such data to in vitro protocols aiming at generating functional human ß-cells from iPSC and human fetal pancreas
Aim 3 (PI: Patrick Collombat; Co-PI: Raphael Scharfmann): To translate such data from in vitro conditions to in vivo mouse settings.

Such synergistic effort should allow us to define innovative ways to increase the functional ß-cell mass.