The role of the vascular niche on transdifferentiated insulin producing cells’ maturation

Regenerative medicine includes the possibility of growing tissues in the laboratory and safely implants them when the body cannot heal itself. We were the first to demonstrate the capacity of generating insulin producing cells by adult liver cells’ transdifferentiation (Autologous Insulin Producing cells-ie AIP cells). This approach allows diabetic patients to be the donors their own therapeutic tissues. Thus, it overcomes both the shortage of organs available from donation, and the transplanted allogeneic organ’s rejection. A major hurdle the field of regenerative medicine faces is that the newly generated cells are usually of heterogenic and immature nature.

The aim of the present study is to unravel the role of the vasculature niche on AIP cells maturation and function both in vitro and upon in vivo implantation.

Our study suggests that vasculature displays a paracrine effect on AIP cells maturation and function; Co-culture of endothelial progenitor cells (EPC) and human mesenchymal stem cell (MSC) improves the AIP cells maturation and function, in vitro. Moreover, co-implantation of AIP cells with EPCs and MSCs promotes vasculature of the implanted cells and increases their survival and function upon sub-Q implantation. Finally, local induction of host vasculature is obligatory and sufficient for implanted AIP cells’ survival and function.

The vascular niche may play a universal role in regenerative medicine, due to its paracrine effects on newly generated organs’ maturation. The capacity to easily promote vascularization in vivo, may allow the implantation of the newly generated tissues in accessible sites in our body.