Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke
Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke
复制标题
DOI：
10.1177/0271678x17731964
复制
发表时间：
2017-09
影响因子：
6.3
通讯作者：
Susumu Yamaguchi;N. Horie;K. Satoh;Takeshi Ishikawa;Tsuyoshi Mori;H. Maeda;Yuhtaka Fukuda;S. Ishizaka;T. Hiu;Y. Morofuji;T. Izumo;N. Nishida;T. Matsuo
中科院分区：
文献类型：
--
作者：
Susumu Yamaguchi;N. Horie;K. Satoh;Takeshi Ishikawa;Tsuyoshi Mori;H. Maeda;Yuhtaka Fukuda;S. Ishizaka;T. Hiu;Y. Morofuji;T. Izumo;N. Nishida;T. Matsuo
细胞移植治疗为改善中风后的损伤提供了巨大的潜力。然而，供体年龄对治疗效果的重要性尚不清楚。我们研究了缺血性卒中移植细胞的再生能力，重点是供体年龄（年轻与老年）。人间充质干细胞（hMSC）体外分泌脑源性神经营养因子的量和体内第7天单核细胞趋化蛋白-1的量均显著高于年轻hMSC。接受年轻hMSC（中风后24小时经动脉）的短暂大脑中动脉闭塞的雄性Sprague-Dawley大鼠与接受老年hMSC的大鼠相比，表现出更好的行为恢复，并预防脑萎缩。梗死周围皮质的组织学分析显示，用年轻hMSC治疗的大鼠具有显著更少的小胶质细胞和更多的被周细胞覆盖的血管。有趣的是，表达Musashi-1的神经干/祖细胞的迁移与星形胶质细胞过程对齐呈正相关，这在年轻的hMSC中更为明显。hMSC的老化可能是影响细胞治疗结果的关键因素，并且年轻hMSC的移植似乎通过抗炎作用、血管成熟和可能由营养因子分泌主导的神经发生提供更好的功能恢复。
Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC. Male Sprague-Dawley rats subjected to transient middle cerebral artery occlusion that received young hMSC (trans-arterially at 24 h after stroke) showed better behavioural recovery with prevention of brain atrophy compared with rats that received old hMSC. Histological analysis of the peri-infarct cortex showed that rats treated with young hMSC had significantly fewer microglia and more vessels covered with pericytes. Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment, which was more pronounced for young hMSC. Aging of hMSC may be a critical factor that affects cell therapy outcomes, and transplantation of young hMSC appears to provide better functional recovery through anti-inflammatory effects, vessel maturation, and neurogenesis potentially by the dominance of trophic factor secretion.