Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice.
Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice.
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DOI：
10.1371/journal.pone.0116009
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kuroda S
中科院分区：
文献类型：
--
作者：
Yamauchi T;Kuroda Y;Morita T;Shichinohe H;Houkin K;Dezawa M;Kuroda S
骨髓基质细胞（BMSC）具有异质性，其治疗作用是多效性的。最近发现，多谱系分化的耐应激 (Muse) 细胞包含几个百分比的 BMSC，能够分化为包括神经元细胞在内的三叶细胞谱系，并充当组织修复细胞。本研究旨在阐明 BMSC 中的 Muse 和非 Muse 细胞如何促进缺血性中风后的功能恢复。人BMSC被分成阶段特异性胚胎抗原3阳性Muse细胞和-阴性非Muse细胞。对免疫缺陷小鼠进行永久性大脑中动脉闭塞，7天后将载体、Muse、非Muse或BMSC（2.5×104个细胞）移植到同侧纹状体中。 BMSC 组和非 Muse 组的运动功能恢复在移植后 21 天时变得明显，但此后达到平台期。在Muse组中，在移植后28天内没有观察到功能恢复，但在移植后35天时功能恢复变得明显。免疫组织化学显示，移植后 42 天，只有 Muse 细胞整合到梗塞周围皮质并分化为表达 Tuj-1 和 NeuN 的细胞，而移植后 42 天，梗塞周围区域中残留的 BMSC 和非 Muse 细胞数量可忽略不计。这些发现强烈表明，Muse 细胞和非 Muse 细胞对组织再生和功能恢复的贡献可能不同。 Muse 细胞可能更负责通过整合到梗塞周围皮层并自发分化为神经元标记阳性细胞来替换丢失的神经元。非 Muse 细胞不会保留在宿主大脑中，并且可能表现出营养作用而不是细胞替代作用。
Bone marrow stromal cells (BMSCs) are heterogeneous and their therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring (Muse) cells are recently identified to comprise several percentages of BMSCs, being able to differentiate into triploblastic lineages including neuronal cells and act as tissue repair cells. This study was aimed to clarify how Muse and non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke. Human BMSCs were separated into stage specific embryonic antigen-3-positive Muse cells and -negative non-Muse cells. Immunodeficient mice were subjected to permanent middle cerebral artery occlusion and received transplantation of vehicle, Muse, non-Muse or BMSCs (2.5×104 cells) into the ipsilateral striatum 7 days later. Motor function recovery in BMSC and non-Muse groups became apparent at 21 days after transplantation, but reached the plateau thereafter. In Muse group, functional recovery was not observed for up to 28 days post-transplantation, but became apparent at 35 days post-transplantation. On immunohistochemistry, only Muse cells were integrated into peri-infarct cortex and differentiate into Tuj-1- and NeuN-expressing cells, while negligible number of BMSCs and non-Muse cells remained in the peri-infarct area at 42 days post-transplantation. These findings strongly suggest that Muse cells and non-Muse cells may contribute differently to tissue regeneration and functional recovery. Muse cells may be more responsible for replacement of the lost neurons through their integration into the peri-infarct cortex and spontaneous differentiation into neuronal marker-positive cells. Non-Muse cells do not remain in the host brain and may exhibit trophic effects rather than cell replacement.
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影响因子：
4.2
作者：
HAMM, RJ;PIKE, BR;JENKINS, LW
通讯作者：
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影响因子：
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通讯作者：
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作者：
Lee, JB;Kuroda, S;Iwasaki, Y
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Iwasaki, Y