Making functional beta-cells from stem cells in a dish

The aim is to develop a novel culture system for human pancreatic cells. Ultimately this platform can be used to investigate the role of vascularisation on human stem cell-derived-pancreatic progenitor maturation. The project is a collaboration between the Leiden University Medical Center and Mimetas B.V, with the support of the DON Foundation.

Diabetes is one of the most prevalent chronic diseases. It affects 450 million individuals worldwide, including 1 million people in the Netherlands. Diabetes is characterised by an increased blood sugar levels. Despite intensive insulin treatment optimal glycemic control is not achieved and patients often develop long-term complications: diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. According to the World Health Organization, diabetes is the seventh leading cause of death (1.6 million deaths directly attributed to diabetes in 2016).

A reduced insulin-producing beta-cell mass is a key factor in the pathogenesis of diabetes. While for decades treatments have focused on symptomatic treatments, i.e. reducing blood sugar levels without targeting the underlying pathophysiology, there is a strong need for alternative therapeutic strategies focusing on replacement of beta-cell mass. New beta-cells can be generated from stem cells in a laboratory. These cells are not fully functional, but they can specialise further upon transplantation in a vascularised environment (in mice). It is not known how this process works, and experiments in animals are very costly and time-consuming. Therefore, the aim is to develop a small scale in vitro culture system (‘organ-on-a-chip’) to investigate the role of vascularisation on beta-cell maturation in a dish. Ultimately this research may lead to the development of the next generation of stem cell-derived cell product, consisting of a vascularised and functional islet microtissue.

Unfortunately, a large part of this project took place during the Covid-19 pandemic, which had major consequences for the research activities. Nevertheless, they managed to perform a number of key experiments, which pave the way  for further optimisation of such platform for human pancreatic cell culture.