A Simple Method to Induce Differentiation of Murine Bone Marrow Mesenchymal Cells to Insulin-producing Cells Using Conophylline and Betacellulin-delta4

Endocrine Journal

Itaru KOJIMA¹  Kazuo UMEZAWA⁵  Satoko YAMADA¹  Toshiyuki TAKEUCHI¹  Etsuko HISANAGA¹  Izumi TAKEI³  Kee-Yong PARK¹  Masaharu SENO⁴  Hiromi HASHIMOTO¹  Masatomo MORI² 

[1] Institute for Molecular & Cellular Regulation;Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine;Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital;Department of Biotechnology, Okayama University Graduate School of Science and Technology;Department of Applied Chemistry, Faculty of Science and Technology, Keio University

关键词: Insulin;    Beta cell;    Differentiation;   

DOI  :  10.1507/endocrj.K07E-173

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(17)Cited-By(18)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.

【 授权许可】

Unknown