Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells.
Ductal structures of the adult pancreas contain stem cells that differentiate into islets of Langerhans. Here, we grew pancreatic ductal epithelial cells isolated from prediabetic adult non-obese diabetic mice in long-term cultures, where they were induced to produce functioning islets containing alpha, beta and delta cells. These in vitro-generated islets showed temporal changes in mRNA transcripts for islet cell-associated differentiation markers, responded in vitro to glucose challenge, and reversed insulin-dependent diabetes after being implanted into diabetic non-obese diabetic mice. The ability to control growth and differentiation of islet stem cells provides an abundant islet source for beta-cell reconstitution in type I diabetes.
Ramiya
V K
VK
Ixion Biotechnology, 13709 Progress Blvd., Box 13, Alachua, Florida 32615, USA.
Maraist
M
M
Arfors
K E
KE
Schatz
D A
DA
Peck
A B
AB
Cornelius
J G
JG
D000818:Animals; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D007515:Islets of Langerhans / Q000098:blood supply / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D018919:Neovascularization, Physiologic; D010183:Pancreatic Ducts / Q000166:cytology* / Q000473:pathology; D011236:Prediabetic State / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*