Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Expert Opin Biol Ther. 2021 Nov;21(11):1411-1427. doi: 10.1080/14712598.2021.1914582. Epub 2021 Apr 26.
Traumatic Spinal Cord Injury (SCI) results from primary physical injury to the spinal cord, which initiates a secondary cascade of neural cell death. Current therapeutic approaches can attenuate the consequences of the primary and secondary events, but do not address the degenerative aspects of SCI. Transplantation of neural stem/progenitor cells (NPCs) for the replacement of the lost/damaged neural cells is suggested here as a regenerative approach that is complementary to current therapeutics.: This review addresses how neurons, oligodendrocytes, and astrocytes are impacted by traumatic SCI, and how current research in regenerative-NPC therapeutics aims to restore their functionality. Methods used to enhance graft survival, as well as bias progenitor cells towards neuronal, oligodendrogenic, and astroglia lineages are discussed. Despite an NPC's ability to differentiate into neurons, oligodendrocytes, and astrocytes in the transplant environment, their potential therapeutic efficacy requires further optimization prior to translation into the clinic. Considering the temporospatial identity of NPCs could promote neural repair in region specific injuries throughout the spinal cord. Moreover, understanding which cells are targeted by NPC-derived myelinating cells can help restore physiologically-relevant myelin patterns. Finally, the duality of astrocytes is discussed, outlining their context-dependent importance in the treatment of SCI.
创伤性脊髓损伤(SCI)是由于脊髓的原发性物理损伤引起的,它引发了神经细胞死亡的继发性级联反应。目前的治疗方法可以减轻原发性和继发性事件的后果,但不能解决 SCI 的退行性方面的问题。这里提出了神经干细胞/祖细胞(NPCs)移植作为一种补充现有治疗方法的再生方法,用于替代丢失/受损的神经细胞:本综述讨论了神经元、少突胶质细胞和星形胶质细胞如何受到创伤性 SCI 的影响,以及再生-NPC 治疗的当前研究如何旨在恢复它们的功能。讨论了用于增强移植物存活的方法,以及将祖细胞偏向神经元、少突胶质细胞和星形胶质细胞谱系的方法。尽管 NPC 在移植环境中能够分化为神经元、少突胶质细胞和星形胶质细胞,但在将其转化为临床应用之前,其潜在的治疗效果需要进一步优化。考虑 NPC 的时空特征可能会促进整个脊髓的特定区域损伤的神经修复。此外,了解 NPC 衍生的髓鞘形成细胞的靶向细胞有助于恢复生理相关的髓鞘模式。最后,讨论了星形胶质细胞的双重性,概述了它们在 SCI 治疗中的上下文依赖性重要性。