A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4

Etsuko Hisanaga, Kee Yong Park, Satoko Yamada, Hiromi Hashimoto, Toshiyuki Takeuchi, Masatomo Mori, Masaharu Seno, Kazuo Umezawa, Izumi Takei, Itaru Kojima

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41 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)535-543
Number of pages9
JournalEndocrine journal
Issue number3
Publication statusPublished - Jul 14 2008



  • Beta cell
  • Differentiation
  • Insulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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