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

FM19G11 and Ependymal Progenitor/Stem Cell Combinatory Treatment Enhances Neuronal Preservation and Oligodendrogenesis after Severe Spinal Cord Injury.
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DOI:
10.3390/ijms19010200
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发表时间:
2018-01-09
影响因子:
5.6
通讯作者:
Moreno-Manzano V
Moreno-Manzano V
中科院分区:
生物学2区
文献类型:
--
作者:
Alastrue-Agudo A;Rodriguez-Jimenez FJ;Mocholi EL;De Giorgio F;Erceg S;Moreno-Manzano V

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脊髓损伤(SCI)缺乏有效的治疗策略。我们先前已经证明,个体化的治疗策略,损伤后脊髓室管膜干/祖细胞移植(EpSPCi)或FM19G11药物治疗,可以诱导脊髓损伤后适度的功能恢复。在这里,已经对联合治疗进行了功能和组织学分析。重度脊髓损伤后,立即髓内注射100万个epSPCi,并经鞘内插管给予FM19G11化合物或二甲基亚砜(DMSO)作为载体对照。与对照组相比,epSPCi和FM19G11联合治疗改善了运动任务,但与单独治疗相比,并未显著提高Basso、Beattie、Bresna han(BBB)的运动分析分数。然而,脊髓损伤和治疗后两个月的组织学分析表明,当我们同时使用epSPCi和FM19G11治疗动物时,通过减少胶质瘢痕的延伸,改善了神经元保存的环境。联合治疗还可通过诱导体内寡突胶质前体细胞的表达而促进少突胶质前体细胞的分化。这些结果表明,联合治疗可能是一种令人兴奋的新治疗方法,可以更有效地恢复严重脊髓损伤后的神经元活动。
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.
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