Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Department of Microbiology, Kindai University, Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
Brain Res. 2019 Jun 1;1712:139-150. doi: 10.1016/j.brainres.2019.01.037. Epub 2019 Feb 2.
We 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.
Induced 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 CD11bCD163 M2 macrophages into the border zone of the cerebral infarction at 4 days post-MCAO (the acute phase).
Our 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 CD11bCD163 M2 macrophages in infarcted lesions.
我们先前建立了一种使用胎牛血清分离和培养人脂肪来源干细胞（hADSCs）的方法，并证明了其对脑梗死的治疗作用。最近，我们修改了培养方法，使用无血清培养基，以便将来用于临床应用。本研究旨在评估无血清培养法诱导的 hADSCs 静脉注射是否会改善脑梗死小鼠的神经行为缺陷。
诱导的 hADSCs 具有间充质干细胞的特征，并能耐受冻融过程。hADSC 给药可改善 MCAO 处理小鼠的神经行为缺陷，并抑制慢性期的脑萎缩。尽管 hADSC 给药不影响血清细胞因子谱，但它减少了脾脏中 CD11b 单核细胞的数量。同时，hADSC 给药可增加 CD11bCD163 M2 巨噬细胞在 MCAO 后 4 天（急性期）向脑梗死边界区的局部积累。
我们的数据表明，hADSCs 的系统给药可以通过调节梗死灶中 CD11bCD163 M2 巨噬细胞介导的急性免疫反应，改善脑梗死发生后的神经行为缺陷。
