Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat.

Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat.
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DOI:
10.3390/ijms150711275
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发表时间:
2014-06-25
影响因子:
5.6
通讯作者:
Jendelová P
Jendelová P
中科院分区:
生物学2区
文献类型:
--
作者:
Urdzíková LM;Růžička J;LaBagnara M;Kárová K;Kubinová Š;Jiráková K;Murali R;Syková E;Jhanwar-Uniyal M;Jendelová P

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间充质干细胞(MSC)移植促进脊髓损伤(SCI)实验模型的功能恢复然而,这种效应背后的机制尚不完全清楚。我们研究了鞘内植入人间充质干细胞对大鼠脊髓球囊压缩性损伤的功能恢复、星形胶质细胞形成和炎症细胞因子水平的影响。移植细胞不能在脊髓病变部位存活;然而,正如Basso, Beattie, and Bresnahan (BBB)和平束试验所证实的那样,msc治疗组的功能恢复得到了增强。形态计量学分析显示,在受损脊髓的颅骨部分,剩余白质的数量明显增加。免疫组化分析显示,骨髓间质干细胞治疗动物的神经胶质瘢痕发生重排。Real-time PCR分析显示Irf5、Mrc1、Fgf2、Gap43和Gfap的表达增加。与盐水处理的对照组相比,将MSCs移植到受损脊髓中可降低tnf - α、IL-4、IL-1β、IL-2、IL-6和IL-12,并增加MIP-1α和RANTES水平。鞘内植入MSCs可减少脊髓损伤后的炎症反应和细胞凋亡,促进功能恢复,调节神经胶质瘢痕形成,而不影响细胞存活。因此,重复施用可延长间充质干细胞诱导的有益效应。
Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1β, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application.
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