Wu Xiao-Hong, Liu Cui-Ping, Xu Kuan-Feng, Mao Xiao-Dong, Zhu Jian, Jiang Jing-Jing, Cui Dai, Zhang Mei, Xu Yu, Liu Chao
Department of Endocrinology, First affiliated hospital of Nanjing Medical University, 300 Guang-zhou Road, Nanjing 210029, Jiangsu Province, China.
World J Gastroenterol. 2007 Jun 28;13(24):3342-9. doi: 10.3748/wjg.v13.i24.3342.
To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat.
BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. Insulin release after glucose challenge was tested with ELISA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry.
BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.
Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro. Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.
研究骨髓间充质干细胞（BM-MSCs）向胰岛样细胞转分化的能力，并观察胰岛样细胞门静脉移植对链脲佐菌素诱导的糖尿病大鼠的治疗效果。
从SD大鼠分离出BM-MSCs，并在特定条件下诱导其分化为胰岛样细胞。通过电子显微镜、逆转录-聚合酶链反应（RT-PCR）、免疫荧光和流式细胞术评估分化情况。用酶联免疫吸附测定（ELISA）检测葡萄糖刺激后的胰岛素释放。然后将同种异体胰岛样细胞经门静脉移植到糖尿病大鼠体内。监测血糖水平，并通过免疫组织化学检测受体肝脏和胰腺中的胰岛激素。
BM-MSCs为球形贴壁单层细胞，高表达CD90、CD29，低表达CD45。诱导后形成典型的胰岛样细胞簇。电子显微镜显示，分化细胞的细胞质内密集排列着分泌颗粒。球形细胞表达胰岛相关基因和激素。诱导后胰岛素阳性细胞占19.8%，平均荧光强度增加2.6倍。细胞分泌少量胰岛素，葡萄糖刺激后增加1.5倍。移植后，胰岛样细胞可定位于肝脏并表达胰岛激素，在第6天至第20天降低糖尿病大鼠的血糖水平。
大鼠BM-MSCs在体外可转分化为胰岛样细胞。胰岛样细胞门静脉移植可减轻糖尿病大鼠的高血糖症。
