Three-Dimensional Spheroid-Cultured Mesenchymal Stem Cells Devoid of Embolism Attenuate Brain Stroke Injury After Intra-Arterial Injection
Three-Dimensional Spheroid-Cultured Mesenchymal Stem Cells Devoid of Embolism Attenuate Brain Stroke Injury After Intra-Arterial Injection
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DOI：
10.1089/scd.2013.0338
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发表时间：
2014-05-01
影响因子：
4
通讯作者：
Wu, Yaojiong
中科院分区：
文献类型：
--
作者：
Guo, Ling;Ge, Jianfeng;Wu, Yaojiong
间充质干细胞(MSCs)在组织修复/再生中的治疗效果因原始特性的丧失和对靶器官的植入不良而受到严重影响。在这项研究中，在单层培养中扩增了几代的人MSCs的多能性和细胞大小在三维(3D)球体培养一段时间后显著恢复。与单层来源的MSCs会导致血栓和失明不同，3D球体来源的MSCs在大鼠颈动脉内注射后不会造成血管阻塞。重要的是，在大鼠大脑中动脉闭塞和再灌流后24小时，颈动脉内注入100万个3D球状MSCs，可使细胞植入病变内，并显著(超过70%)缩小梗塞面积，并恢复神经功能。此外，球形MSCs的增强作用与MSCs向神经元的分化显著增加以及梗死灶周围区内源性神经胶质纤维酸性蛋白阳性神经前体细胞的数量显著增加相一致。然而，相似处理的单层MSCs导致了适度的功能改善。我们的结果表明，3D MSCs与颈动脉内给药相结合，可能是MSCs治疗中风的一种新途径。
The therapeutic effect of mesenchymal stem cells (MSCs) in tissue repair/regeneration is substantially dampened by the loss of primitive properties and poor engraftment to target organs. In this study, the multipotency and cell sizes of human MSCs, which had been expanded in monolayer culture for several passages, were dramatically restored after an episode of three-dimensional (3D) spheroid culture. Unlike MSCs derived from monolayer, which caused embolism and blindness, MSCs derived from 3D spheroids did not cause vascular obstructions, after intra-carotid artery infusion in rats. Importantly, intra-carotid infusion of 1 million 3D spheroid MSCs in rats 24 h after middle cerebral artery occlusion and reperfusion resulted in engraftment of the cells into the lesion and significant (over 70%) reduction of infarct size along with restoration of neurologic function. Moreover, the enhanced effect of spheroid MSCs was coincided with significantly increased differentiation of the MSCs into neurons and markedly increased number of endogenous glial fibrillary acidic protein-positive neural progenitors in the peri-infarct boundary zone. However, the similarly administered monolayer MSCs resulted in a modest functional improvement. Our results suggest that 3D MSCs, in combination with intra-carotid delivery, may represent a novel therapeutic approach of MSCs for stroke.