About the institute

Project Plan

Although there is no cure to type-1 diabetics (T1Ds), if monitored properly (glucose levels) and treated by daily injections of insulin, many patients can live a fairly normal life. However, with age the frequency of complications such as kidney failure and blindness due to vascular complications dramatically worsens the situation for patients (suffering and lifespan) and their families. What is more, a small population (few %) of patients responds poorly to the available treatment, which eventually may lead to premature death (“brittle diabetes”). Importantly, when these patients receive donor islet of Langerhans transplants their uncontrolled glucose fluctuations dramatically improves. This provides encouraging proof-of-concept data that cell-replacement therapy in T1D is a way forward.

The scarcity of cadaveric islets, has sparked a search for a new, in principle limitless, supply of stable and well-characterized functional (glucose-responsive) beta cells. Human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), fulfill these criteria due to their ability to both self-renew and differentiate into insulin-producing cells that produce similar amounts of insulin and share functional features of mature beta cells. Obviously, even if these cells could be mass-produced the challenges with the auto-immunity remain. This challenge could be addressed either by immunosuppression or by administering the cells within a device that prevents interactions with immune cells. The latter will also lower the risks for cancer to arise from remaining undifferentiated hPSCs. Nevertheless, there is considerable excitement in moving towards clinical trials to for the first time test the safety and efficacy of beta cells generated from hPSCs.

The overall objective of this project is to solve some of the bottle-necks in up-scaled production of mature beta cells from hPSCs and to manufacture GMP certified stem cell derived beta cells to initiate the first phase 1 trial.
The overall objective of this project (2017-21) is to prepare for the first phase 1 trial by cGMP adapting our current differentiation protocol of hESCs into glucose-responsive beta cells. The project will be a collaboration with TUMCells.

Milestones towards the first phase 1 study using human pluripotent stem cell-derived insulin+ cells

M1: Identify a GMP cell line for the phase I clinical trial.
M2: Establish working and master cell banks of the selected GMP hPSC cell line and perform validation studies.
M3: To GMP adapt the current differentiation protocol for generation of hPSC-derived beta cells.
M4: QC establishment, pre-validation activities including animal studies, and obtaining regulatory approval for the phase I trial.
M5: GMP production of hESC-derived insulin cells for a small phase I study.