Cell therapy for type 1 diabetes

Abstract

Cell therapy in the form of human islet transplantation has been a successful form of treatment for patients with type 1 diabetes for over 10 years, but is significantly limited by lack of suitable donor material. A replenishable supply of insulin-producing cells has the potential to address this problem; however to date success has been limited to a few preclinical studies. Two of the most promising strategies include differentiation of embryonic stem cells and induced pluripotent stem cells towards insulin-producing cells and transdifferentiation of acinar or other closely related cell types towards β-cells. Here, we discuss recent progress and challenges that need to be overcome in taking cell therapy to the clinic.

Figure 1.

Strategies for generating a replenishable supply of beta cells. (A) Schematic representation of the stepwise differentiation of pluripotent cells towards β-cells in vitro. The final maturation stages of beta cell development remain challenging to replicate under in vitro conditions. (B) Procedure for reprogramming the exocrine tissue resultant from the islet isolation procedure towards functional beta cells. After being placed in culture, the exocrine phenotype is maintained by inhibiting EMT. Reprogramming towards functional beta cells is subsequently achieved by overexpression of pancreatic transcription factors and growth factors.