Institutt for biomedisin

BBB seminar: Helge Ræder

The use of hiPSCs-derived pancreatic cells in diabetes disease modeling and prospects for diabetes cell therapy


Helge Ræder
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, and Department of Pediatrics, Haukeland University Hospital, Bergen

Since the discovery by Shinya Yamanaka and co-workers of a method to reprogram terminally differentiated cells such as skin cells into induced pluripotent stem cells (iPSCs) a decade ago, a plethora of disease models have emerged for a variety of disorders based on the subsequent targeted differentiation of these cells by the timely addition of chemical compounds. Now, also novel cell therapies are emerging in Phase I/II-trials based on autologous (iPSC-based) or allogenic (iPSC- or human embryonic stem cell (hESC)-based) cell therapy products obtained through targeted differentiation of stem cells towards the desired cell product. In diabetes, such therapies are particularly promising since transplantation of encapsulated insulin-secreting cells may potentially provide cells that automatically read the blood glucose levels and provide insulin in appropriate doses without the need for glucose sensors or insulin injections. Furthermore, the encapsulation may prevent the rejection of the cell product by immune mechanisms related to the primary disease process (autoimmunity in type 1 diabetes) and by transplantation of allogenic material.

We have reprogrammed skin fibroblasts from patients with monogenic diabetes and generated human iPSCs (hiPSCs), which we have subsequently differentiated into pancreatic beta-like cells. In the process of targeted differentiation we have noted increasing cell heterogeneity which may affect not only the efficacy of glucose sensing in the pancreatic beta-like cells but also may introduce a risk for iatrogenic cancer in future cell therapy products used in diabetes.

Our ongoing work is focused on optimizing the current differentiation protocols, on exploring cell and animal models for mutation-specific effects, and on establishing means to survey cancer-risk in hiPSC-derived pancreatic beta-like cells.

Chairperson: Rolf K. Reed <rolf.reed@uib.no>, Department of Biomedicine