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自组装肽与神经干细胞/祖细胞的协同作用促进颈脊髓损伤的组织修复和前肢功能恢复。

Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury.

机构信息

Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.

Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada; Institutes of Medical Science, University of Toronto, University Health Network Toronto, ON M5S 1A8, Canada.

出版信息

Biomaterials. 2014 Mar;35(9):2617-29. doi: 10.1016/j.biomaterials.2013.12.019. Epub 2014 Jan 7.

Abstract

While neural stem/progenitor cells (NPCs) show promise for traumatic spinal cord injury (SCI), their efficacy in cervical SCI remains to be established. Moreover, their application to SCI is limited by the challenges posed by the lesion including the glial scar and the post-traumatic cavitation. Given this background, we sought to examine the synergistic effect of self-assembling peptide (SAP) molecules, designed to optimize the post-traumatic CNS microenvironment, and NSCs in a clinically-relevant model of contusive/compressive cervical SCI. We injected K2(QL)6K2 (QL6) SAPs into the lesion epicenter 14 days after bilateral clip compression-induced cervical SCI in rats, combined with simultaneous transplantation of neural stem/progenitor cells (NPCs) intraspinally adjacent to the lesion epicenter. The QL6 SAPs reduced the volume of cystic cavitation in the spinal cord lesion. Simultaneously engrafted NPCs preserved motor neurons and attenuated perilesional inflammation. The combination of QL6 and NPCs promoted forelimb neurobehavioral recovery and was associated with significant improvement in forelimb print area and stride length. In summary, we report for the first time histologic and functional benefits in a clinically-relevant model of cervical SCI through the synergistic effects of combined SAP and NPCs.

摘要

虽然神经干细胞/祖细胞 (NPCs) 在创伤性脊髓损伤 (SCI) 中显示出前景,但它们在颈椎 SCI 中的疗效仍有待确定。此外,它们在 SCI 中的应用受到包括神经胶质瘢痕和创伤后空洞在内的损伤带来的挑战的限制。有鉴于此,我们试图在撞击/压迫性颈椎 SCI 的临床相关模型中,研究自组装肽 (SAP) 分子与 NPCs 的协同作用。我们在双侧夹压诱导的大鼠颈椎 SCI 后 14 天,将 K2(QL)6K2 (QL6) SAP 注射到损伤中心,同时将神经干细胞/祖细胞 (NPCs) 移植到损伤中心附近的脊髓内。QL6 SAP 减少了脊髓损伤中的囊性空洞体积。同时移植的 NPC 保留了运动神经元并减轻了损伤周围的炎症。QL6 和 NPC 的联合使用促进了前肢神经行为的恢复,并与前肢印迹面积和步幅的显著改善相关。总之,我们首次通过 SAP 和 NPC 的协同作用,在颈椎 SCI 的临床相关模型中报告了组织学和功能上的益处。

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