Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury
Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury
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DOI：
10.1016/j.biomaterials.2013.12.019
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发表时间：
2014-03-01
期刊：
影响因子：
14
通讯作者：
Fehlings, Michael G.
中科院分区：
文献类型：
--
作者：
Iwasaki, Motoyuki;Wilcox, Jared T.;Fehlings, Michael G.
虽然神经干/祖细胞（NPCs）在创伤性脊髓损伤（SCI）中显示出前景，但其在颈椎脊髓损伤中的疗效仍有待确定。此外，它们在脊髓损伤中的应用受到损伤带来的挑战，包括神经胶质疤痕和创伤后空化。考虑到这一背景，我们试图在一个与临床相关的挫伤/压缩性颈椎脊髓损伤模型中，研究旨在优化创伤后中枢神经系统微环境的自组装肽（SAP）分子和NSCs的协同作用。我们在大鼠双侧夹压性颈椎损伤后第14天将K2(QL)6K2 (QL6) SAPs注射到病变中心，同时在病变中心附近的椎管内同时移植神经干/祖细胞（NPCs）。QL6 SAPs减少脊髓病变囊性空化的体积。同时，移植的NPCs保存了运动神经元，减轻了病灶周围的炎症。QL6和NPCs联合使用可促进前肢神经行为恢复，并显著改善前肢印面积和步长。总之，我们首次报道了通过联合SAP和NPCs的协同作用，在临床相关的颈椎脊髓损伤模型中组织学和功能方面的益处。(C) 2013 Elsevier Ltd.版权所有。
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. (C) 2013 Elsevier Ltd. All rights reserved.