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FM19G11 与室管膜祖/干细胞联合治疗增强严重脊髓损伤后的神经元保护和少突胶质细胞发生。

FM19G11 and Ependymal Progenitor/Stem Cell Combinatory Treatment Enhances Neuronal Preservation and Oligodendrogenesis after Severe Spinal Cord Injury.

机构信息

Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, 46012 Valencia, Spain.

Stem Cell Therapies in Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain.

出版信息

Int J Mol Sci. 2018 Jan 9;19(1):200. doi: 10.3390/ijms19010200.

Abstract

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. We have previously shown that individual therapeutic strategies, transplantation of ependymal stem/progenitor cells of the spinal cord after injury (epSPCi) or FM19G11 pharmacological treatment, induce moderate functional recovery after SCI. Here, the combination of treatments has been assayed for functional and histological analysis. Immediately after severe SCI, one million epSPCi were intramedullary injected, and the FM19G11 compound or dimethyl sulfoxide (DMSO) (as the vehicle control) was administrated via intrathecal catheterization. The combination of treatments, epSPCi and FM19G11, improves locomotor tasks compared to the control group, but did not significantly improve the Basso, Beattie, Bresnahan (BBB) scores for locomotor analysis in comparison with the individual treatments. However, the histological analysis of the spinal cord tissues, two months after SCI and treatments, demonstrated that when we treat the animals with both epSPCi and FM19G11, an improved environment for neuronal preservation was generated by reduction of the glial scar extension. The combinatorial treatment also contributes to enhancing the oligodendrocyte precursor cells by inducing the expression of Olig1 in vivo. These results suggest that a combination of therapies may be an exciting new therapeutic treatment for more efficient neuronal activity recovery after severe SCI.

摘要

脊髓损伤(SCI)缺乏有效的治疗策略。我们之前已经表明,在损伤后移植脊髓室管膜干细胞/祖细胞(epSPCi)或 FM19G11 药物治疗等单一治疗策略可以在 SCI 后诱导适度的功能恢复。在这里,已经对联合治疗进行了功能和组织学分析。在严重 SCI 后立即通过脑室内导管将一百万 epSPCi 注入脊髓内,并给予 FM19G11 化合物或二甲亚砜(DMSO)(作为载体对照)。与对照组相比,联合治疗 epSPCi 和 FM19G11 可改善运动任务,但与单独治疗相比,在运动分析的 Basso、Beattie、Bresnahan(BBB)评分方面并没有显著改善。然而,SCI 和治疗两个月后的脊髓组织组织学分析表明,当我们用 epSPCi 和 FM19G11 联合治疗动物时,通过减少神经胶质瘢痕的延伸,为神经元的保存创造了一个更好的环境。联合治疗还通过体内诱导 Olig1 的表达来促进少突胶质前体细胞的增强。这些结果表明,联合治疗可能是一种令人兴奋的新的治疗方法,可更有效地促进严重 SCI 后神经元活动的恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb3f/5796149/835e3564b24f/ijms-19-00200-g001.jpg

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