Rat umbilical cord blood cells attenuate hypoxic-ischemic brain injury in neonatal rats.
Rat umbilical cord blood cells attenuate hypoxic-ischemic brain injury in neonatal rats.
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DOI：
10.1038/srep44111
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发表时间：
2017-03-10
影响因子：
4.6
通讯作者：
Higashi Y
中科院分区：
文献类型：
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作者：
Nakanishi K;Sato Y;Mizutani Y;Ito M;Hirakawa A;Higashi Y
越来越多的证据表明人脐带血细胞（human umbilical cord blood cells，hUCBC）对缺氧缺血性脑损伤（hypoxic-ischemic brain injury，HI）具有良好的治疗作用。然而，使用hUCBCs治疗这种损伤的功效是可变的，并且潜在的机制仍然难以捉摸。在这里，我们研究了其有效性，使用体视学分析在同种异体系统，以检查是否腹腔注射来自UCBCs的绿色荧光蛋白（GFP）转基因大鼠的细胞可以改善新生大鼠的脑损伤。HI事件后三周，估计残留脑体积较大，运动功能改善更多的细胞注射大鼠比对照组（PBS治疗）大鼠。注射后9天，在脑中几乎检测不到GFP阳性细胞（注射细胞的0.0057%）。虽然脑中60%的GFP阳性细胞为Iba 1阳性，但这些细胞中没有一个为NeuroD或DCX阳性。而海马中增殖细胞的数量增加，激活的小胶质细胞/巨噬细胞减少，M2小胶质细胞/巨噬细胞的比例增加，在细胞注射大鼠的同侧半球。这些结果表明，腹膜内注射来源于UCBCs的细胞可以改善HI损伤，可能是通过内源性反应，而不是通过提供来源于注射的干细胞的分化神经元。
Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic–ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells.