Beta-cell replacement therapy is the only option to restore normoglycemia without an increased risk of hypoglycemia in patients with type 1 diabetes. A shortage of donor organs limits the wider application of beta-cell replacement therapy. Therefore, alternative cell sources are necessary to generate sufficient beta-cell mass for future therapy. In collaboration with the Leiden University Medical Center we explore the use of adult human pancreatic progenitor cells to reach this goal. The expertise in the Hubrecht Institute expanding and differentiating stem/progenitor cells from endodermal origin using 3-dimensional culture systems is important to move this field ahead. The ultimate goal is to generate sufficient functional beta-cell mass that can be used for innovative cell therapy in diabetes. Other projects in our group focus on the role of the gut in glucose homeostasis. In the gut there are neuroendocrine L-cells that augment insulin secretion. Using the 3-dimensional culture system of human and mouse intestinal tissue we try to understand how L-cell dynamics plays a role in normal physiology and diabetes. Also the role of the glycocalyx as an important component of the microvasculature in islet function and complications is studied.
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