Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors into Functional Islets Capable of Treating Pre-existing Diabetes in Mice

Diabetes is a chronic debilitating disease that results from in-sufficient production of insulin from pancreatic b-cells. Islet cell replacement can effectively treat diabetes but is currently severely limited by the reliance upon cadaveric donor tissue. We have de-veloped a protocol to efficiently differentiate commercially avail-able human embryonic stem cells (hESCs) in vitro into a highly enriched PDX1+ pancreatic progenitor cell population that further develops in vivo to mature pancreatic endocrine cells. Immature pancreatic precursor cells were transplanted into immunodeficient mice with streptozotocin-induced diabetes, and glycemia was ini-tially controlled with exogenous insulin. As graft-derived insulin levels increased over time, diabetic mice were weaned from exog-enous insulin and human C-peptide secretion was eventually reg-ulated by meal and glucose challenges. Similar differentiation of pancreatic precursor cells was observed after transplant in immu