RGM.20.012 – Patient-specific beta-cell replacement therapy using pluripotent stem cells for the treatment of diabetes mellitus

Route: Regenerative medicine: game changer moving to broad areas of application

Cluster question: 100 How can we use cells, stem cells, and biomaterials to engineer and regenerate tissues and organs?

In the Netherlands more than 100,000 people have severe deficiency of insulin-producing beta-cells, such as in type 1 diabetes (T1D), and need insulin therapy to survive. However, despite intensive insulin treatment optimal glycemic control is not achieved resulting in long-term vascular complications and poor quality of life. Thus, diabetes causes a huge financial burden to society. Therefore, there is an unmet clinical and societal need for new therapies to completely normalize glycemic control.
Beta-cell replacement by either pancreas or islet transplantation is the only therapy that normalizes glycemia without a risk of hypoglycemia. However, current therapy is limited by the need of immunosuppression and a shortage of organ donors. Therefore, a renewable source of insulin-producing cells is a key step to develop novel therapies. We focus on pluripotent stem cells (PSC) as the next-generation cell source for beta-cell replacement therapy.
Although we are now able to differentiate PSC into insulin-producing cells, a major drawback to test the long-term functionality of these cells in patients with T1D, is rejection due to alloreactivity for third-party cells and recurrence of autoimmunity. Therefore we propose to generate a proof-of-concept study generating patient-specific iPSC for patients that have severe diabetes due to a total pancreatectomy. Using our current GMP infrastructure, and expertise in human beta-cell biology and clinical beta-cell transplantation, we will: generate clinical-grade iPSC lines for 3 pancreatectomised patients with a total pancreatectomy, apply optimised differentiation protocols, test the functionality and safety of the insulin-producing cells in vitro and in vivo in immunodeficient diabetic mice, and prepare the investigational medicinal product dossier for clinical transplantation. Without allo-and autoreactivity, we can now unequivocally determine the potential of PSC-derived beta-cell replacement therapy. This will set the stage for wider application in patients with T1D.


GMP, insulin, Pluripotent stem cells


Organisation Leiden University Medical Center (LUMC)
Name Prof.dr. E. (Eelco) de Koning
E-mail e.dekoning@lumc.nl
Website http://www.einthovenlaboratory.com/onderzoeken/islet-group-research/