Transdifferentiation of human adipose tissue-derived stromal cells into insulin-producing clusters.
Type 1 diabetes mellitus is caused by autoimmune destruction of insulin-producing beta cells. The major obstacle to transplantation of insulin-producing cells to cure the disease is the limited source of these cells. To overcome this problem, we describe here a multistep protocol for generation of insulin-producing islet-like clusters from human adipose tissue-derived stromal cells (ADSCs). Analysis using reverse transcription polymerase chain reaction detected enhanced expression of various pancreatic genes during the differentiation of ADSCs. Immunofluorescence analysis revealed functional similarities between cells derived from ADSCs and pancreatic islet cells, i.e., the presence of insulin- and C-peptide-coexpressing cells in the clusters and glucagon expression on the cell surface. The glucose challenge tests revealed the production of insulin, and such production was regulated via physiological signaling pathways. Our insulin-producing cells derived from ADSCs could be potentially used for cell therapy of type 1 diabetes mellitus.
Okura
Hanayuki
H
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Komoda
Hiroshi
H
Fumimoto
Yuichi
Y
Lee
Chun-Man
CM
Nishida
Toshirou
T
Sawa
Yoshiki
Y
Matsuyama
Akifumi
A
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D054338:Cell Transdifferentiation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000378:metabolism; D017154:Stromal Cells
D007328:Insulin; D010187:Pancreatic Hormones