Placenta-derived multipotent stem cells induced to differentiate into insulin-positive cells
Placenta-derived multipotent stem cells induced to differentiate into insulin-positive cells
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DOI：
10.1016/j.bbrc.2007.03.157
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Ku, Hung-Hai
中科院分区：
文献类型：
--
作者：
Chang, Chia-Ming;Kao, Chung-Lan;Ku, Hung-Hai
在本研究中，我们成功地从人胎盘组织中分离PDMSC。RT-PCR结果显示PDMSC保留了原始胚胎Oct-4和Nanog的遗传特征。采用无血清培养基和诱导培养基培养4周，单层的PDMSC逐渐形成三维球体（SB-PDMSC）。通过使用实时RT-PCR，观察到Pdx 1以及Sox 17和Foxa 2基因的早期mRNA表达在SB-PDMSC中显著激活，随后是成熟胰腺相关基因（胰岛素、胰高血糖素和生长抑素）的表达。ELISA检测进一步证实了SB-PDMSC的高胰岛素含量，并通过相应的胰岛素分泌水平证明了葡萄糖依赖性。在链脲佐菌素预处理的裸鼠的移植研究中，进一步观察到SB-PDMSC处理组中的正常细胞的恢复。总之，这些结果表明PDMSC是功能良好的胰岛素阳性细胞的诱导分化的极好来源。这些源自PDMSC的胰岛素产生细胞的潜力也通过体外分泌胰岛素和体内有效控制血糖水平的证明而在功能上得到证明。(c)2007爱思唯尔公司All rights reserved.
In the present study, we successfully isolated PDMSCs from human placental tissues. The RT-PCR results show that PDMSCs preserved the genetic characteristics of the primitive embryonic stage-Oct-4 and Nanog. By using serum-free medium supplemented essential growth factors and induction medium culture for 4 weeks, a monolayer of spindle-like PDMSCs gradually formed 3D spheroid bodies (SB-PDMSCs). By using real-time RT-PCR, early mRNA expressions of Pdx1, as well as the Sox17 and Foxa2 genes, were observed to be significantly activated in SB-PDMSCs, followed by the expression of mature pancreas-related genes (insulin, glucagon, and somatostatin). The high insulin content of SB-PDMSCs was further confirmed by ELISA assay, and the glucose dependency was demonstrated by the corresponding insulin secretion level. In a transplantation study of streptozotocin-pretreated nude mice, the restoration of normoglycemia in the SB-PDMSC treated group was further observed. In conclusion, these results indicate that PDMSCs are an excellent source for the induced differentiation of well-functioning insulin-positive cells. The potential of these insulin producing cells derived from PDMSCs was also demonstrated functionally by the demonstration of secreted insulin in vitro and effective control of blood glucose levels in vivo. (c) 2007 Elsevier Inc. All rights reserved.