Stem Cell–Derived Islets: Next Steps for Histologic and Functional Assessment During Development as a Cellular Therapy for the Treatment of Diabetes

Left: In vivo islet differentiation during normal embryonic and fetal development. Right: In vitro islet development of hESCs or inducible pluripotent stem cells (iPSC) designed to mimic normal differentiation (adapted from Jennings et al. [3]). In the report by Pepper et al. (9), no mesodermal or acinar cell tissue was identified following in vivo maturation of transplanted stage 4 PECs into functional islet grafts; however, all grafts contained mucinous ductal tissue organized in cystic structures by 200 days. Whether further in vitro differentiation and transplantation of, for example, stage 7 pancreatic islet cells may eliminate the development of ductal tissue during in vivo maturation requires additional long-term studies.