Urdzíková Lucia Machová, Růžička Jiří, LaBagnara Michael, Kárová Kristýna, Kubinová Šárka, Jiráková Klára, Murali Raj, Syková Eva, Jhanwar-Uniyal Meena, Jendelová Pavla
Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague 14220, Czech Republic.
Department of Neurosurgery, New York Medical College, Valhalla, NY 10595, USA.
Int J Mol Sci. 2014 Jun 25;15(7):11275-93. doi: 10.3390/ijms150711275.
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.
间充质干细胞（MSC）移植可改善脊髓损伤（SCI）实验模型中的功能恢复；然而，这种作用背后的机制尚未完全明确。我们利用球囊诱导的脊髓压迫损伤，研究了鞘内植入人MSC对大鼠功能恢复、星形胶质细胞增生及炎性细胞因子水平的影响。移植的细胞并未在脊髓损伤部位存活；然而，经Basso、Beattie和Bresnahan（BBB）评分及平板光束试验证实，MSC治疗组的功能恢复得到了增强。形态学分析显示，损伤脊髓头部剩余的白质数量显著更多。对损伤部位的免疫组织化学分析表明，MSC治疗的动物中胶质瘢痕发生了重排。实时PCR分析显示，Irf5、Mrc1、Fgf2、Gap43和Gfap的表达增加。与生理盐水处理的对照组相比，将MSC移植到损伤脊髓中可降低TNFα、IL-4、IL-1β、IL-2、IL-6和IL-12的水平，并提高MIP-1α和RANTES的水平。鞘内植入MSC可减轻SCI后的炎症反应和细胞凋亡，改善功能恢复并调节胶质瘢痕形成，无论细胞是否存活。因此，重复应用可能会延长MSC应用所诱导的有益作用。
