Adipose-derived stem cell therapy inhibits the deterioration of cerebral infarction by altering macrophage kinetics
Adipose-derived stem cell therapy inhibits the deterioration of cerebral infarction by altering macrophage kinetics
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DOI：
10.1016/j.brainres.2019.01.037
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发表时间：
2019-06
期刊：
影响因子：
2.9
通讯作者：
Kotaro Tatebayashi;Toshinori Takagi;M. Fujita;N. Doe;T. Nakagomi;T. Matsuyama;S. Yoshimura
中科院分区：
文献类型：
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作者：
Kotaro Tatebayashi;Toshinori Takagi;M. Fujita;N. Doe;T. Nakagomi;T. Matsuyama;S. Yoshimura
我们先前建立了一种利用胎牛血清分离和培养人脂肪干细胞的方法，并展示了其对脑梗塞的治疗作用。最近，我们对培养方法进行了改进，使用了无血清培养基以用于未来的临床应用。本研究旨在评价静脉注射无血清培养法诱导的hADSCs是否能改善脑梗塞小鼠的神经行为缺陷。结果诱导的hADSCs具有间充质干细胞的特性，并能经受冻融过程。HADSC给药改善了MCAO治疗小鼠的神经行为缺陷，并抑制了慢性期的脑萎缩。虽然hADSC给药对小鼠血清细胞因子谱无影响，但能降低小鼠脾CD11b+单核细胞的数量。同时，在脑梗塞后4 (急性期)，hADSC可增加脑梗塞边缘区CD11b+CD163+M2巨噬细胞的局部积聚。
IntroductionWe previously established a method to isolate and culture human adipose-derived stem cells (hADSCs) using fetal bovine serum and showed the therapeutic impact on cerebral infarction. Recently, we modified the culture method with the use of serum-free media for future clinical applications. This study aims to evaluate whether intravenous administration of hADSCs induced by the serum-free culture method would improve neurobehavioral deficits in mice with cerebral infarction.ResultsInduced hADSCs possessed the characteristics of mesenchymal stem cells and withstood a freeze-thaw process. hADSC administration improved neurobehavioral deficits in MCAO-treated mice and suppressed brain atrophy at the chronic phase. Although hADSC administration did not affect serum cytokine profiles, it decreased the number of CD11b+monocytes in the spleen. Concomitantly, hADSC administration increased the local accumulation of CD11b+CD163+M2 macrophages into the border zone of the cerebral infarction at 4 days post-MCAO (the acute phase).DiscussionOur data indicate that the systemic administration of hADSCs can improve the neurobehavioral deficits that occur after cerebral infarction by modulating the acute immune response mediated by CD11b+CD163+M2 macrophages in infarcted lesions.