Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats.

Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats.
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修饰的人骨髓衍生的基质细胞的移植对大鼠脑缺血的治疗作用。

DOI:
10.1111/cns.13947
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发表时间:
2022-12
影响因子:
5.5
通讯作者:
--
中科院分区:
医学1区
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--
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SB 623细胞是用Notch 1胞内结构域转染的人骨髓基质细胞。在这项研究中,我们研究了潜在的再生机制的立体定向移植SB 623细胞在大鼠实验性急性缺血性中风。制备对照组、空胶囊(EC)组、SB 623细胞组(SB 623)、微囊化SB 623细胞(eSB 623)组。在第0天进行短暂性大脑中动脉闭塞(MCAO),并在MCAO后24 h,将中风大鼠移植到设想的缺血半暗带。对改良神经系统严重程度评分(mNSS)进行评价,并进行组织学评价。在mNSS中,与其他组相比,SB 623和eSB 623组显示出显著改善。组织学分析显示SB 623和eSB 623组的梗死面积减少。在eSB 623组中,在室管膜下区检测到稳健的细胞活力和神经发生,与所有其他组相比显著增加。SB 623细胞包被或未包被对缺血性脑卒中均有治疗作用。封装的SB 623细胞显示出增强的神经发生和胶囊内的活力增加。这项研究揭示了移植的SB 623细胞的分泌功能的机制,但不是细胞-细胞相互作用,主要介导细胞在缺血性中风中的功能益处。本研究证实了SB 623细胞包被和未包被对大鼠急性缺血性脑卒中模型均有治疗作用。微囊化的SB 623细胞比未微囊化的SB 623细胞增强神经发生并且存活更长时间。
SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell–cell interaction as primarily mediating the cells' functional benefits in ischemic stroke. This study demonstrated SB623 cells with or without encapsulation exerted therapeutic effects on acute ischemic stroke model of rats. Encapsulated SB623 cells enhanced neurogenesis and survived longer than unencapsulated SB623 cells.
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