In vivo characterization of transplanted human embryonic stem cell-derived pancreatic endocrine islet cells.

Objectives: Islet-like clusters (ILCs), differentiated from human embryonic stem cells (hESCs), were characterized both before and after transplantation under the kidney capsule of streptozotocin-induced diabetic immuno-incompetent mice. Materials and methods: Multiple independent ILC preparations ( n = 8) were characterized by immunohistochemistry, flow cytometry and cell insulin content, with six preparations transplanted into diabetic mice ( n = 42), compared to controls, which were transplanted with either a human fibroblast cell line or undifferentiated hESCs ( n = 28). Results: Prior to transplantation, ILCs were immunoreactive for the islet hormones insulin, C-peptide and glucagon, and for the ductal epithelial marker cytokeratin-19. ILCs also had cellular insulin contents similar to or higher than human foetal islets. Expression of islet and pancreas-specific cell markers was maintained for 70 days post-transplantation. The mean survival of recipients was increased by transplanted ILCs as compared to transplanted human fibroblast cells ( P < 0.0001), or undifferentiated hESCs ( P < 0.042). Graft function was confirmed by secretion of human C-peptide in response to an oral bolus of glucose. Conclusions: hESC-derived ILC grafts continued to contain cells that were positive for islet endocrine hormones and were shown to be functional by their ability to secrete human C-peptide. Further enrichment and maturation of ILCs could lead to generation of a sufficient source of insulin-producing cells for transplantation into patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]