Stem-Cell-Based Therapies for Improving Islet Transplantation Outcomes in Type 1 Diabetes

Beta-cell replacement by human islets or whole pancreas offers a life-saving therapeutic remedy for patients suffering from type 1 diabetes, providing considerable advantages with respect to diminishing total daily insulin dose and lowering frequencies of debilitating hypoglycemic reactions as well as preventing chronic micro- and macrovascular complications. Although remarkable progress has been made in this area, several hurdles remain, hampering its wide-spread applicability. Such hurdles include a limiting supply of islets, the necessity of several donors to achieve enough islet mass for insulin independence, and graft failure because of metabolic pressure, continued autoimmunity, alloimmunity, high concentrations of immunosuppressive drugs as well as oxidative stress caused by hypoxia or inflammation. On the other hand, the islet transplant procedure provides the possibility to undertake multiple practical and beneficial manipulations of the beta cells before engraftment with the intention to reach improved graft survival results. Here, we have focused on the current status of various obstacles in islet transplantation and on the potential of (stem)cell-based treatments able to stimulate islet graft outcome in pre-clinical and clinical transplantation settings in which specific attention is given to the engraftment-enhancing and immunomodulatory potential of various types of stem cells.status: publishe