title: A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4.
abstract: The present study was conducted to establish a method to induce differentiation of bone marrow (MB)-derived mesenchymal cells into insulin-producing cells. When mouse BM-derived mesenchymal cells were cultured for 60 days in medium containing 10% fetal calf serum and 25 mM glucose, they expressed insulin. Addition of activin A and betacellulin (BTC) accelerated differentiation, and immunoreactive insulin was detected 14 days after the treatment. Insulin-containing secretory granules were observed in differentiated cells by electron microscopy. Treatment of BM-derived mesenchymal cells with conophylline (CnP) and BTC-delta4 further accelerated differentiation, and mRNA for insulin was detected 5 to 7 days after the treatment. Mesencymal cells treated with CnP and BTC-delta4 responded to a high concentration of glucose and secreted mature insulin. When these cells were transplanted into streptozotocin-treated mice, they markedly reduced the plasma glucose concentration, and the effect continued for at least 4 weeks. These results indicate an efficacy of the combination of CnP and BTC-delta4 in inducing differentiation of BM-derived mesenchymal cells into insulin-producing cells.
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hisanaga
authors.forename: Kee-Yong
authors.initials: KY
authors.lastname: Park
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Izumi
authors.initials: I
authors.lastname: Takei
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D000818:Animals; D066259:Betacellulin; D001786:Blood Glucose / Q000032:analysis; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D014748:Vinca Alkaloids / Q000494:pharmacology*
chemical_list: D066259:Betacellulin; D001786:Blood Glucose; C587852:Btc protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D014748:Vinca Alkaloids; C099167:conophylline