Diabetes research institute

Beta Cell Differentiation


Project leader

Valeria Sordi


Beta cells in the pancreas secrete insulin and control blood glucose level. Beta cell mass deficiency characterizes both type 1 diabetes, in which beta cells are destroyed by an autoimmune attack, and type 2 diabetes, in which beta cells are dysfunctional and undergo apoptosis. Clinical and experimental islet transplantation demonstrate that it is possible to replace beta cell mass, restoring normoglycemia. Unfortunately, this approach is strongly limited by the scarcity of donors and the need for lifelong immunosuppression of transplant recipients. A new infinite source of insulin producing beta cells would then represent a major advance in the field.

Research activity

We generate new functional beta cells from pluripotent stem cells. Differentiation of ESC/iPSC into beta cells in vitro follows pancreatic developmental stages, from pluripotency to definitive endoderm, then to posterior foregut cells, pancreatic endoderm, endocrine progenitors and finally to insulin-producing mature beta cells. We set up protocols, optimized for several pluripotent cell lines, established all the relevant read-outs, compared the final product with human islets from organ donors, analysed the transcriptome of the cell during differentiation at single cell level. Moreover, in the unit we transplant stem cell-derived beta in cells in diabetic mouse model, follow the function in vivo and investigate strategies to improve the engraftment and survival, like co- transplantation of feeder cells, modulation of graft microenvironment, or to control the immune reaction to the graft.

Generation of beta cells from stem cells is also a tool for the study of beta cell physiology and pathology, for instance it provides tools for disease modelling of genetic disease with mutations affecting the beta cells, like monogenic diabetes of the adult (MODY) or Wolfram syndrome.