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人骨髓源性克隆间充质干细胞移植减少大鼠脊髓损伤模型中纤维瘢痕的形成。

Transplantation of human bone marrow-derived clonal mesenchymal stem cells reduces fibrotic scar formation in a rat spinal cord injury model.

机构信息

Department of Biomedical Sciences, Inha University College of Medicine, Incheon, Republic of Korea.

Veterans Medical Research Institute, VHS Medical Center, Seoul, Republic of Korea.

出版信息

J Tissue Eng Regen Med. 2018 Feb;12(2):e1034-e1045. doi: 10.1002/term.2425. Epub 2017 Jun 9.

DOI:10.1002/term.2425
PMID:28112873
Abstract

This study aimed to evaluate the therapeutic effect on tissue repair and scar formation of human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) homogeneously isolated by using a subfractionation culturing method, in comparison with the non-clonal MSCs (hMSCs), in a rat spinal cord injury (SCI) model. The SCI was made using a vascular clip at the T9 level. Cells were transplanted into the lesion site 3 days after injury. A functional test was performed over 4 weeks employing a BBB score. Rats were killed for histological analysis at 3 days, 1 week and 4 weeks after injury. The transplantation of hMSCs and hcMSCs significantly reduced lesion size and the fluid-filled cavity at 4 weeks in comparison with the control group injected with phosphate buffered saline (PBS) (p < 0.01). Transplantation of hcMSCs showed more axons reserved than that of hMSCs in the lesion epicentre filled with non-neuronal tissues. In addition, hMSCs and hcMSCs clearly reduced the inflammatory reaction and intraparenchymal hemorrhaging, compared with the PBS group. Interestingly, hcMSCs largely decreased Col IV expression, one of the markers of fibrotic scars. hcMSCs yielded therapeutic effects more than equal to those of hMSCs on the SCI. Both hMSCs and hcMSCs created an increase in axon regeneration and reduced scar formation around the SCI lesion. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

本研究旨在评估同种异体分离培养的人骨髓源性克隆间充质干细胞(hcMSCs)在大鼠脊髓损伤(SCI)模型中的组织修复和瘢痕形成的治疗效果,并与非克隆间充质干细胞(hMSCs)进行比较。SCI 通过 T9 水平的血管夹制作。损伤后 3 天将细胞移植到损伤部位。在 4 周的时间内通过 BBB 评分进行功能测试。在损伤后 3 天、1 周和 4 周处死大鼠进行组织学分析。与注射磷酸盐缓冲盐水(PBS)的对照组相比,hMSCs 和 hcMSCs 的移植显著减少了 4 周时的损伤面积和充满液体的腔(p < 0.01)。在充满非神经元组织的损伤中心,hcMSCs 移植的保留轴突比 hMSCs 移植的多。此外,与 PBS 组相比,hMSCs 和 hcMSCs 明显减轻了炎症反应和脑实质出血。有趣的是,hcMSCs 大大降低了 Col IV 的表达,Col IV 是纤维化瘢痕的标志物之一。hcMSCs 在 SCI 上的治疗效果优于 hMSCs。hMSCs 和 hcMSCs 都增加了 SCI 损伤周围轴突的再生,并减少了瘢痕形成。版权所有© 2017 约翰威立父子公司

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