Falnikar Aditi, Li Ke, Lepore Angelo C
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University Medical College, 900 Walnut Street, JHN 469, Philadelphia, PA 19107, United States.
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University Medical College, 900 Walnut Street, JHN 469, Philadelphia, PA 19107, United States.
Brain Res. 2015 Sep 4;1619:91-103. doi: 10.1016/j.brainres.2014.09.037. Epub 2014 Sep 22.
Replacement of lost and/or dysfunctional astrocytes via multipotent neural stem cell (NSC) and lineage-restricted neural progenitor cell (NPC) transplantation is a promising therapeutic approach for traumatic spinal cord injury (SCI). Cell transplantation in general offers the potential to replace central nervous system (CNS) cell types, achieve remyelination, deliver missing gene products, promote and guide axonal growth, modulate the host immune response, deliver neuroprotective factors, and provide a cellular substrate for bridging the lesion site, amongst other possible benefits. A host of cell types that differ in their developmental stage, CNS region and species of derivation, as well as in their phenotypic potential, have been tested in a variety of SCI animal models. Historically in the SCI field, most pre-clinical NSC and NPC transplantation studies have focused on neuronal and oligodendrocyte replacement. However, much less attention has been geared towards targeting astroglial dysfunction in the inured spinal cord, despite the integral roles played by astrocytes in both normal CNS function and in the diseased nervous system. Despite the relative lack of studies, cell transplantation-based targeting of astrocytes dates back to some of the earliest transplant studies in SCI animal models. In this review, we will describe the history of work involving cell transplantation for targeting astrocytes in models of SCI. We will also touch on the current state of affairs in the field, as well as on important future directions as we move forward in trying to develop this approach into a viable strategy for SCI patients. Practical issues such as timing of delivery, route of transplantation and immunesuppression needs are beyond the scope of this review. This article is part of a Special Issue entitled SI: Spinal cord injury.
通过多能神经干细胞(NSC)和谱系受限神经祖细胞(NPC)移植来替代丢失和/或功能失调的星形胶质细胞,是创伤性脊髓损伤(SCI)一种很有前景的治疗方法。一般来说,细胞移植有可能替代中枢神经系统(CNS)细胞类型、实现髓鞘再生、递送缺失的基因产物、促进和引导轴突生长、调节宿主免疫反应、递送神经保护因子以及为桥接损伤部位提供细胞基质等诸多潜在益处。许多在发育阶段、CNS区域、来源物种以及表型潜能方面存在差异的细胞类型,已在各种SCI动物模型中进行了测试。在SCI领域的历史上,大多数临床前NSC和NPC移植研究都集中在神经元和少突胶质细胞的替代上。然而,尽管星形胶质细胞在正常CNS功能和患病神经系统中都发挥着不可或缺的作用,但针对损伤脊髓中星形胶质细胞功能障碍的研究却少得多。尽管相关研究相对较少,但基于细胞移植靶向星形胶质细胞的研究可以追溯到SCI动物模型中一些最早的移植研究。在这篇综述中,我们将描述在SCI模型中针对星形胶质细胞进行细胞移植的工作历史。我们还将探讨该领域的现状,以及在努力将这种方法发展成为SCI患者可行策略的过程中未来的重要方向。诸如递送时间、移植途径和免疫抑制需求等实际问题不在本综述范围内。本文是名为“脊髓损伤”特刊的一部分。