Derivation of hepato-pancreatic intermediate progenitor cells from a clonal mesenchymal stem cell line of rat bone marrow origin.
We have recently established a clonal mesenchymal stem cell line (rBM25/S3) from adult rat bone marrow. The cells have practically unlimited proliferation capacity (over 300 PDL), maintaining multipotency for differentiation. In the present study, we examined the potential for rBM25/S3 cells to differentiate into insulin-secreting cells. When cultured in the presence of HGF and FGF-4 on Matrigel, rBM25/S3 cells expressed genes specific to pancreatic beta-cells as well as those specific to hepatocytes. They still maintained proliferation capacity with a doubling time of approximately 30 h. These hepato-pancreatic intermediate progenitor cells, but not the original undifferentiated rBM25/S3 cells, were induced by the overexpression of PDX-1 to produce significant amounts of insulin in a manner responding to glucose concentration in medium. The present culture system indicates a direction for further studies aimed at the realization of cell transplantation therapy for type I diabetes mellitus.
Masaka
Takuro
T
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-Chou, Okayama, Japan.
Miyazaki
Masahiro
M
Du
Gang
G
Hardjo
Marhaen
M
Sakaguchi
Masakiyo
M
Takaishi
Mikiro
M
Kataoka
Ken
K
Yamamoto
Kazuhide
K
Huh
Nam-Ho
NH
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002999:Clone Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010179:Pancreas / Q000166:cytology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology*
D002096:C-Peptide; D007328:Insulin