Decellularized peripheral nerve supports Schwann cell transplants and axon growth following spinal cord injury.

Decellularized peripheral nerve supports Schwann cell transplants and axon growth following spinal cord injury.
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DOI:
10.1016/j.biomaterials.2018.05.049
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发表时间:
2018-09
期刊:
影响因子:
14
通讯作者:
Bunge MB
Bunge MB
中科院分区:
工程技术1区
文献类型:
--
作者:
Cerqueira SR;Lee YS;Cornelison RC;Mertz MW;Wachs RA;Schmidt CE;Bunge MB

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雪旺细胞(SC)移植作为脊髓损伤(SCI)修复的一种策略已被广泛研究。SC具有神经保护作用,并促进轴突再生和髓鞘形成。尽管如此,植入后发生大量SC死亡,这限制了治疗效果。使用细胞外基质(ECM)衍生的基质,如Matrigel,支持移植的SC存活和轴突生长,从而改善运动功能。由于临床翻译需要适当的基质,我们在这里测试使用脱细胞可注射外周神经(iPN)基质。与仅损伤的对照相比,将iPN中的SC植入挫伤病变中不会改变免疫细胞浸润。iPN植入物更大,包含的SC有髓轴突是Matrigel移植物的两倍。SC/iPN动物在BBB运动测试中表现与SC/Matrigel组一样好,并且在4周时在网格行走中的错误较少,在8周时均衡。这种临床相关的iPN基质具有免疫耐受性,并支持移植物内的SC存活和轴突生长,这一事实为改善SCI后SC治疗的疗效提供了高度转化的可能性。据我们所知,这是第一次评价可注射PN基质以提高SCI修复中细胞SC移植的疗效。
Schwann cell (SC) transplantation has been comprehensively studied as a strategy for spinal cord injury (SCI) repair. SCs are neuroprotective and promote axon regeneration and myelination. Nonetheless, substantial SC death occurs post-implantation, which limits therapeutic efficacy. The use of extracellular matrix (ECM)-derived matrices, such as Matrigel, supports transplanted SC survival and axon growth, resulting in improved motor function. Because appropriate matrices are needed for clinical translation, we test here the use of an acellular injectable peripheral nerve (iPN) matrix. Implantation of SCs in iPN into a contusion lesion did not alter immune cell infiltration compared to injury only controls. iPN implants were larger and contained twice as many SC-myelinated axons as Matrigel grafts. SC/iPN animals performed as well as the SC/Matrigel group in the BBB locomotor test, and made fewer errors on the grid walk at 4 weeks, equalizing at 8 weeks. The fact that this clinically relevant iPN matrix is immunologically tolerated and supports SC survival and axon growth within the graft offers a highly translational possibility for improving efficacy of SC treatment after SCI. To our knowledge, it is the first time that an injectable PN matrix is being evaluated to improve the efficacy of cell SC transplantation in SCI repair.
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