In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells.
A major obstacle to successful islet transplantation for both type 1 and 2 diabetes is an inadequate supply of insulin-producing tissue. In vitro transdifferentiation of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) into insulin-producing cells could provide an abundant source of cells for this procedure. For this study, we isolated and characterized human UCB-MSCs and induced them in vitro to differentiate into islet-like cell clusters using a 15-day protocol based on a combination of high-glucose, retinoic acid, nicotinamide, epidermal growth factor, and exendin-4. These clusters appeared about 9 days after pancreatic differentiation; expressed pancreatic beta-cell markers, including insulin, glucagon, Glut-2, PDX1, Pax4, and Ngn3; and could synthesize and secrete functional islet proteins at the end of the inducing protocol. The insulin-positive cells accounted for (25.2-3.36)% of whole induced cells. Although insulin secretion of those insulin-producing cells did not respond to glucose challenge very well, human UCB-MSCs have the ability to differentiate into islet-like cells in vitro and may be a potential new source for islet transplantation.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medicine University, Harbin, China.
Feng
F
Gao
De-Quan
DQ
Wu
Yan-Hua
YH
Hu
Guang-Xin
GX
Jin
Guo-Dong
GD
Li
Tie-Wei
TW
Sun
Fu-Jun
FJ
Li
D015153:Blotting, Western; D002096:C-Peptide / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014470:Umbilical Cord / Q000166:cytology* / Q000187:drug effects
D002096:C-Peptide; D007328:Insulin; D005934:Glucagon; D005947:Glucose