Would pancreas duct-epithelium-derived stem/progenitor cells enhance islet allograft survival by means of islets recruitment and tolerance induction in Edmonton protocol era?

SummaryRates of insulin independence at 1 year with current Edmonton protocol are impressive. However, obstacles such as the restricted availability of donor pancreas, coupled with recipient’s pharmacologic immunosuppression, have lent strong impetus to the search for new sources of insulin-producing cells. But work with stem cells has not yet produced cells with the phenotype of true β cells. Recently the data have shown that the presence of duct-epithelium in clinical islet transplantation may improve the long-term metabolic outcome. The underlying mechanisms are not well understood. The pancreatic duct-epithelium has been considering as a pool of pancreatic stem/progenitor cells, cytokeratin-19 positive stem cells, which have been proved to be capable of differentiating into endocrine cells and inducing immune tolerance. Based on these findings, we speculate that pancreatic stem/progenitor cells derived from ductal epithelium may enhance islet allograft survival through two aspects: islet recruitment and tolerance induction. The proposition may have clues on the further improvement in clinical islet transplantation long-term outcome.