Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential
Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential
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具有改善治疗潜力的去分化重编程间充质干细胞
DOI：
10.1002/stem.764
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发表时间：
2011-12-01
期刊：
影响因子：
5.2
通讯作者：
Chan, Hsiao Chang
中科院分区：
文献类型：
--
作者：
Liu, Yang;Jiang, Xiaohua;Chan, Hsiao Chang
干细胞移植已被证明可以改善退行性和缺血性疾病的功能结局。然而，移植细胞的低体内存活和分化潜力限制了它们的总体有效性，从而限制了临床应用。在这里，我们表明，在体外诱导神经元分化和去分化后，在撤出的外源性因素，间充质干细胞（MSC）来自骨髓，这已经致力于神经元谱系，恢复到原始细胞群（去分化的MSC）保留干细胞的特性，但表现出重编程的表型不同于他们原来的同行。在治疗方面，去分化的MSC在体外和体内均表现出与未操作的MSC相比增强的细胞存活和更高的神经元分化功效，在新生儿缺氧缺血性脑损伤大鼠模型中具有显著改善的认知功能。bcl-2家族蛋白和microRNA-34 a的表达增加似乎是产生这种先前未定义的干细胞群体的重要机制，这可能提供具有改善的治疗功效的新治疗策略。干细胞2011;29：2077-2089
Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and microRNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy. STEM CELLS 2011;29:2077-2089