Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

摘要

Diabetes mellitus is a disease that can lead to dangerously high blood sugar levels, causing numerous complications such as heart disease, glaucoma, skin disorders, kidney disease, and nerve damage. In healthy individuals, beta cells in the pancreas produce a hormone called insulin, which stimulates cells in the liver, muscles and fat to take up glucose from the blood. However, this process is disrupted in people with diabetes, who either have too few pancreatic beta cells (type 1 diabetes) or do not respond appropriately to insulin (type 2 diabetes). All patients with type 1 diabetes, and some with type 2, must inject themselves regularly with insulin, but this does not always fully control the disease. Some type 1 patients have been successfully treated with beta cells transplanted from deceased donors, but there are not enough donor organs available for this to become routine. Thus, intensive efforts worldwide are focused on generating insulin-producing cells in the lab from human stem cells. However, the cells produced in this way can give rise to tumors. Now, Lee et al. have shown that duct cells, which make up about 30% of the human pancreas, can be converted into cells capable of producing and secreting insulin. Ductal cells obtained from donor pancreases were first separated from the remaining tissue and grown in cell culture. Viruses were then used to introduce genes that reprogrammed the ductal cells so that they acquired the ability to make, process and store insulin, and to release it in response to glucose—hallmark features of functional beta cells. As well as providing a potential source of cells for use in transplant or cell conversion therapies for diabetes, the ability to grow and maintain human pancreatic ductal cells in culture may make it easier to study other diseases that affect the pancreas, including pancreatitis, cystic fibrosis, and adenocarcinoma.