There is an urgent need for cell-based therapies to treat insulin-dependent diabetes mellitus. Stem cells are a potential source for the bioengineering of pancreatic islet microorgans for insulin replacement therapy in patients with insulin-dependent diabetes mellitus. This project will therefore explore the potential of embryonic stem cells for a cell-based therapy.

Background
	Diabetes mellitus is a major health problem affecting between 20 and 30 million people in the European Union. It imposes a heavy burden of morbidity and premature mortality. Diabetes and its complications also incur a large and steadily increasing financial cost which is approaching 10 % of the annual health care budget. Transplantation of a donor human pancreas or pancreatic islets offers, in theory, a cure for the disease. However, availability of donor tissue for transplantation is limited. Due to the paucity of pancreas organ supply, transplantation is possible only in a few very severely ill diabetic patients. Therefore this project will explore the potential to bioengineer pancreatic islet microorgans of differentiated stem cell origin for insulin replacement therapy in order to overcome this limitation.
Description, impact and results
	The aim of this project is to engineer pancreatic islet microorgans (so-called pseudoislets) suitable for insulin replacement therapy in diabetes. To achieve this goal, gene therapy technologies to bioengineer glucose-responsive insulin-secreting surrogate cells of stem cell origin will be applied. These cells will be aggregated in organized microorgans similar to normal pancreatic islets. Insulin-secreting cells show their optimal functional capacity when organized in the form of pancreatic islets of Langerhans. They operate a machinery of regulated biosynthesis and secretion of insulin in response to physiological glucose stimulation. The bioengineered pseudoislets will replace the destroyed pancreatic islets of the diabetic patient. These microorgans should be suitable substitutes to restore the function of the destroyed pancreatic islets in a diabetic individual. A combination of the bioengineering of insulin-secreting surrogate cells with techniques for generation of a pancreatic islet microorgan represents a highly innovative experimental approach. This Cell Factory concept applied to insulin-producing cells offers an innovative and realistic perspective for a curative cell therapy of a majority of diabetic patients.
Working partnerships
	A consortium of seven university institutions and a SME industrial partner from Germany, the United Kingdom, Spain, Belgium and Switzerland collaborates in this project. It comprises scientific competence in the field of stem cell biology, organ bioengineering, pancreatic beta cell molecular and cellular biology.