In vivo characterization of transplanted human embryonic stem cell-derived pancreatic endocrine islet cells.
Cell Prolif
; 41(6): 843-858, 2008 Dec.
Article
in En
| MEDLINE
| ID: mdl-19040565
ABSTRACT
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 ANDMETHODS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Islets of Langerhans Transplantation
/
Islets of Langerhans
/
Embryonic Stem Cells
/
Endocrine Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Prolif
Year:
2008
Document type:
Article
Affiliation country:
United States