Differentiation of insulin-producing cells from human neural progenitor cells.
BACKGROUND
Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin.


RESULTS
Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs). During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors.


CONCLUSIONS
Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.
Hori
Yuichi
Y
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
Gu
Xueying
X
Xie
Xiaodong
X
Kim
Seung K
SK
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D020869:Gene Expression Profiling; D005947:Glucose / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells
D007328:Insulin; D005947:Glucose