Diabetes Mellitus The success of islet cell and pancreas transplantation provides proof of concept for a cell-based approach for type I diabetes. However, the demand for donor pancreata far exceeds the number available, and maintenance of long-term graft survival remains a problem. The search for a renewable source of stem cells capable of regenerating pancreatic islets has therefore been intensive. Pancreatic βcell turnover occurs in the normal pancreas, although the source of the new βcells is controversial. Attempts to promote endogenous regenerative processes have not yet been successful, but this remains a potentially viable approach. A number of different cell. | Chapter 067. Applications of Stem Cell Biology in Clinical Medicine Part 3 Diabetes Mellitus The success of islet cell and pancreas transplantation provides proof of concept for a cell-based approach for type I diabetes. However the demand for donor pancreata far exceeds the number available and maintenance of long-term graft survival remains a problem. The search for a renewable source of stem cells capable of regenerating pancreatic islets has therefore been intensive. Pancreatic 0cell turnover occurs in the normal pancreas although the source of the new 0cells is controversial. Attempts to promote endogenous regenerative processes have not yet been successful but this remains a potentially viable approach. A number of different cell types are candidates for use in stem cell replacement including ES cells hepatic progenitor cells pancreatic ductal progenitor cells and bone marrow stem cells. Successful therapy will depend on developing a source of cells that can be amplified and have the ability to synthesize store and release insulin when it is required primarily in response to changes in the glucose level. The proliferative capacity of the replacement cells must be tightly regulated to avoid excessive expansion of 0cell numbers with the consequent development of hyperinsulinemia hypoglycemia and the cells must avoid immune rejection. Although ES cells can be differentiated into cells that produce insulin these cells have relatively low insulin content and a high rate of apoptosis and they generally lack the capacity to normalize blood glucose in diabetic animals. Thus ES cells have not yet been useful for the large-scale production of differentiated islet cells. During embryogenesis the pancreas liver and gastrointestinal tract are all derived from the anterior endoderm and transdifferentiation of the pancreas to liver and vice versa has been observed in certain pathologic conditions. Multipotential stem cells also reside within gastric glands and intestinal .
