A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4
A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4
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DOI：
10.1507/endocrj.k07e-173
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发表时间：
2008-06-01
影响因子：
2
通讯作者：
Kojima, Itaru
中科院分区：
文献类型：
--
作者：
Hisanaga, Etsuko;Park, Kee-Yong;Kojima, Itaru
本研究旨在建立一种诱导骨髓间充质细胞向胰岛素生成细胞分化的方法。小鼠脑源性间充质细胞在含有10%胎牛血清和25 mM葡萄糖的培养基中培养60天，细胞表达胰岛素。激活素A和β细胞素（BTC）的加入加速了分化，治疗14天后检测到免疫反应性胰岛素。电镜观察分化细胞中含有胰岛素的分泌颗粒。用conophylline （CnP）和BTC-delta4处理脑源性间充质细胞进一步加速分化，并在处理后5 ~ 7天检测到胰岛素mRNA。CnP和BTC-delta4处理的间充质细胞对高浓度葡萄糖有反应并分泌成熟胰岛素。当将这些细胞移植到经链脲佐菌素处理的小鼠体内时，它们显著降低了血浆葡萄糖浓度，并且这种效果持续了至少4周。这些结果表明，CnP和BTC-delta4联合使用可诱导脑源性间充质细胞向胰岛素生成细胞分化。
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.