The Adult Mouse and Human Pancreas Contain Rare Multipotent Stem Cells that Express Insulin

The search for putative precursor cells within the pancreas has been the focus of extensive research. Previously, we identified rare pancreas-derived multipotent precursor (PMP) cells in the mouse with the intriguing capacity to generate progeny in the pancreatic and neural lineages. Here, we establish the embryonic pancreas as the developmental source of PMPs through lineage-labeling experiments. We also show that PMPs express insulin and can contribute to multiple pancreatic and neural cell types in vivo. In addition, we have isolated PMPs from adult human islet tissue that are also capable of extensive proliferation, self-renewal, and generation of multiple differentiated pancreatic and neural cell types. Finally, both mouse and human PMP-derived cells ameliorated diabetes in transplanted mice. These findings demonstrate that the adult mammalian pancreas contains a population of insulin + multipotent stem cells and suggest that these cells may provide a promising line of investigation toward potential therapeutic benefit. ► PMPs express insulin and are derived from the embryonic PDX-1 + pancreatic lineage ► Insulin + precursors contribute to multiple pancreatic and neural lineages in vivo ► Human PMPs exist within islet tissue, capable of generating new functional β cells ► Mouse and human PMP-derived cells ameliorate diabetes in transplanted mice