Open AccessIn vivo characterization of transplanted human embryonic stem cell‐derived pancreatic endocrine islet cells
Author(s) -
Eshpeter A.,
Jiang J.,
Au M.,
Rajotte R. V.,
Lu K.,
Lebkowski J. S.,
Majumdar A. S.,
Korbutt G. S.
Publication year - 2008
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2008.00564.x
Subject(s) - transplantation , islet , biology , embryonic stem cell , enteroendocrine cell , stem cell , pancreas , insulin , medicine , endocrinology , streptozotocin , hormone , endocrine system , diabetes mellitus , microbiology and biotechnology , biochemistry , gene
. 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.