Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats
Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats
复制标题
DOI：
10.1016/j.brainres.2008.06.087
复制
发表时间：
2008-09-10
期刊：
影响因子：
2.9
通讯作者：
Kim, Seung Hyun
中科院分区：
文献类型：
--
作者：
Koh, Seong-Ho;Kim, Kyung Suk;Kim, Seung Hyun
在本研究中，我们研究了植入的人脐带间充质干细胞（hUC-MSC）对缺血性中风的神经保护作用和机制。 hUC-MSCs 从人脐带的内皮/内皮下层分离并培养。体外神经元分化诱导后20天，约77.4%的接种hUC-MSC表现出神经元形态特征，并表达TU-20、Trk A、NeuN和NF-M等神经元细胞标志物。然而，电生理检查未检测到功能活跃的神经元类型通道。在体外神经元分化之前、期间或之后一天，hUC-MSC 产生粒细胞集落刺激因子、血管内皮生长因子、胶质细胞系源性神经营养因子和脑源性神经营养因子。在一项体内研究中，将 hUC-MSC 植入免疫抑制的缺血性中风大鼠的受损半球，与对照大鼠相比，改善了神经行为功能并减少了梗塞体积。植入三周后，大部分植入的hUC-MSCs存在于受损的半球中；其中一些细胞表达可检测水平的神经元特异性标记物。相对于对照组，hUC-MSC植入组海马estin表达增加。由于hUC-MSCs在形态上分化为神经元细胞并能够产生神经营养因子，但尚未成为功能活跃的神经元细胞，因此神经行为功能的改善和梗死体积的减少可能与hUC-MSCs的神经保护作用有关，而不是与宿主神经元和植入的hUC-MSCs之间形成新网络有关。 (C) 2008 Elsevier B.V. 保留所有权利。
In the present study, we examined the neuroprotective effects and mechanisms of implanted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in ischemic stroke. hUC-MSCs were isolated from the endothelial/subendothelial layers of the human umbilical cord and cultured. Twenty days after the induction of in vitro neuronal differentiation, about 77.4% of the inoculated hUC-MSCs displayed morphological features of neurons and expressed neuronal cell markers like TU-20, Trk A, NeuN, and NF-M. However, functionally active neuronal type channels were not detected by electrophysiological examination. Before, during, or one day after in vitro neuronal differentiation, the hUC-MSCs produced granulocytecolony stimulating factor, vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor. In an in vivo study, implantation of the hUC-MSCs into the damaged hemisphere of immunosuppressed ischemic stroke rats improved neurobehavioral function and reduced infarct volume relative to control rats. Three weeks after implantation, most of the implanted hUC-MSCs were present in the damaged hemisphere; some of these cells expressed detectable levels of neuron-specific markers. estin expression in the hippocampus was increased in the hUC-MSC-implanted group relative to the control group. Since the hUC-MSCs were both morphologically differentiated into neuronal cells and able to produce neurotrophic factors, but had not become functionally active neuronal cells, the improvement in neurobehavioral function and the reduction of infarct volume might be related to the neuroprotective effects of hUC-MSCs rather than the formation of a new network between host neurons and the implanted hUC-MSCs. (C) 2008 Elsevier B.V. All rights reserved.