14-P007 Differentiation of human embryonic stem cells towards renal progenitors

ing transplantation with adult mouse donor splenocytes, with the donor splenocytes forming replacement islets. However, the failure of other groups to reproduce these findings has led to increased scrutiny of the role of the spleen for such a purpose. Using a chick-quail chimaera model of pancreatic organogenesis, we show that the developing avian spleen is able to differentiate into insulin-producing cells in vitro through islet mesenchyme-to-epithelial transition (iMET). We show evidence that the splenic mesenchyme is reprogrammed to express the pancreatic islet genes Pdx-1 and Isl-1. The splenic mesenchymal transcription factor Tlx-1 is completely down-regulated during this process, indicating that this tissue is reprogrammed from a splenic to pancreatic endocrine fate. Finally, an attempt is made to augment splenic iMET through the addition of a Wnt agonist. These findings indicate that the spleen may be an ideal tissue source for future bench-to-bedside translational strategies to reverse diabetes.