The anti-apoptotic and neuro-protective effects of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) on acute optic nerve injury is transient
The anti-apoptotic and neuro-protective effects of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) on acute optic nerve injury is transient
复制标题
DOI：
10.1016/j.brainres.2013.07.037
复制
发表时间：
2013-09-26
期刊：
影响因子：
2.9
通讯作者：
Cai, Jiping
中科院分区：
文献类型：
--
作者：
Chen, Meilan;Xiang, Zhenghua;Cai, Jiping
视网膜神经节细胞（RGC）的进行性死亡是视神经损伤后不可逆视力损害的主要原因。目前临床上仍缺乏有效的治疗方法来恢复视功能。维持视力和RGC功能的可能途径包括防止RGC死亡和/或促进受损RGC的再生。以往的研究表明，间充质干细胞（mesenchymal stem cells，MSCs）对缺血性皮质和脊髓损伤具有神经保护作用，但MSCs是否对视神经损伤有保护作用尚不清楚。在本研究中，我们将人脐带血来源的间充质干细胞（hUCB-MSCs）移植到成年大鼠的玻璃体腔中，并研究其抗凋亡和促神经保护作用的可能能力。采用荧光金颗粒（FG）逆行追踪RGCs，caspase-3免疫组化和末端dUTP缺口末端标记（TUNEL）法检测细胞凋亡。苏木精-伊红（HE）染色观察视网膜形态学变化。生长相关蛋白43（GAP-43），轴突再生的一个既定的标志物，被用来可视化随着时间的推移再生过程。在我们的实验中还监测了负责炎症和免疫应答的P2 X7受体（P2 X7 R）的表达。我们发现，hUCB-MSC移植显著减少细胞凋亡，促进早期RGCs的存活。然而，这种保护是短暂的，最终不能保护RGCs免于死亡。与细胞凋亡检测结果相一致，hUCB-MSC移植组大鼠P2 X7 R在移植早期也明显降低，但移植终末与对照组相比无明显差异。因此，我们的结果表明，hUCB-MSCs在成年大鼠急性视神经损伤的早期具有抗凋亡、促神经再生和抗炎作用，但最终不能阻止RGCs死亡。(c)2013爱思唯尔有限公司版权所有。
Progressive death of retinal ganglion cells (RGCs) is a major cause of irreversible visual impairment after optic nerve injury. Clinically, there are still no effective treatments for recovering the visual function at present. The probable approaches to maintain the vision and RGCs function involve in preventing RGCs from death and/or promoting the regeneration of damaged RGCs. Previous studies have shown that mesenchymal stem cells (MSCs) take neuroprotective effects on ischemia-induced cortical and spinal cord injury, however, whether MSCs have a beneficial effect on the optical nerve injury is not clearly determined. In present study, we transplanted MSCs derived from human umbilical cord blood (hUCB-MSCs) into the vitreous cavity of adult rats and investigated the probable capacity of anti-apoptosis and pro-neuroprotective effects on RGCs. RGCs were retrogradely traced by fluorescent gold particles (FG); cellular apoptosis was investigated by caspase-3 immunohistochemistry and terminal dUTP nick end labeling (TUNEL) staining. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of the retina. Growth associated protein 43 (GAP-43), an established marker for axonal regeneration, was used to visualize the regenerative process over time. Expression of P2X7 receptors (P2X7R), which are responsible for inflammatory and immune responses, was also monitored in our experiments. We found that the hUCB-MSC transplantation significantly decreased cellular apoptosis and promoted the survival of RGCs in early phase. However, this protection was transient and the RGCs could not be protected from death in the end. Consistent with apoptosis detection, P2X7R was also significantly decreased in hUCB-MSC transplanted rats in the early time but without obvious difference to the rats from control group in the end. Thus, our results imply that hUCB-MSCs take anti-apoptotic, pro-neuroregenerative and anti-inflammatory effects in the early time for acute optic nerve injury in adult rats but could not prevent RGCs from death eventually. (c) 2013 Elsevier B.V. All rights reserved.