Unlocking the Paradoxical Endogenous Stem Cell Response after Spinal Cord Injury,STEM CELLS

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Unlocking the Paradoxical Endogenous Stem Cell Response after Spinal Cord Injury
STEM CELLS ( IF 4.0 ) Pub Date : 2019-10-24 , DOI: 10.1002/stem.3107
Laureen D Hachem _{1,

2} , Andrea J Mothe ₁ , Charles H Tator _{1,

2}

Affiliation

Nearly a century ago, the concept of the secondary injury in spinal cord trauma was first proposed to explain the complex cascade of molecular and cellular events leading to widespread neuronal and glial cell death after trauma. In recent years, it has been established that the ependymal region of the adult mammalian spinal cord contains a population of multipotent neural stem/progenitor cells (NSPCs) that are activated after spinal cord injury (SCI) and likely play a key role in endogenous repair and regeneration. How these cells respond to the various components of the secondary injury remains poorly understood. Emerging evidence suggests that many of the biochemical components of the secondary injury cascade which have classically been viewed as deleterious to host neuronal and glial cells may paradoxically trigger NSPC activation, proliferation, and differentiation thus challenging our current understanding of secondary injury mechanisms in SCI. Herein, we highlight new findings describing the response of endogenous NSPCs to spinal cord trauma, redefining the secondary mechanisms of SCI through the lens of the endogenous population of stem/progenitor cells. Moreover, we outline how these insights can fuel novel stem cell‐based therapeutic strategies to repair the injured spinal cord.

中文翻译：

解锁脊髓损伤后矛盾的内源性干细胞反应

近一个世纪前，脊髓外伤继发性损伤的概念首次被提出来解释导致外伤后广泛的神经元和神经胶质细胞死亡的分子和细胞事件的复杂级联反应。近年来，已经确定成年哺乳动物脊髓的室管膜区域包含一群多能神经干/祖细胞 (NSPC)，这些细胞在脊髓损伤 (SCI) 后被激活，可能在内源性修复中起关键作用和再生。这些细胞如何对继发性损伤的各种成分做出反应仍然知之甚少。新出现的证据表明，继发性损伤级联反应的许多生化成分通常被认为对宿主神经元和神经胶质细胞有害，但可能会矛盾地触发 NSPC 激活，增殖和分化，从而挑战我们目前对 SCI 继发性损伤机制的理解。在此，我们重点介绍了描述内源性 NSPC 对脊髓创伤反应的新发现，通过内源性干/祖细胞群的视角重新定义了 SCI 的继发机制。此外，我们概述了这些见解如何推动基于干细胞的新型治疗策略来修复受伤的脊髓。

更新日期：2019-10-24

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