Therapeutically targeting astrocytes with stem and progenitor cell transplantation following traumatic spinal cord injury.
Therapeutically targeting astrocytes with stem and progenitor cell transplantation following traumatic spinal cord injury.
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DOI：
10.1016/j.brainres.2014.09.037
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发表时间：
2015-09-04
期刊：
影响因子：
2.9
通讯作者：
Lepore, Angelo C.
中科院分区：
文献类型：
--
作者：
Falnikar, Aditi;Li, Ke;Lepore, Angelo C.
通过多能神经干细胞（NSC）和谱系限制性神经前体细胞（NPC）移植替代丢失和/或功能障碍的星形胶质细胞是创伤性脊髓损伤（SCI）的一种有希望的治疗方法。细胞移植通常提供了替代中枢神经系统（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、调节宿主免疫应答、递送神经保护因子和提供用于桥接病变部位的细胞基质的潜力，以及其他可能的益处。许多细胞类型在其发育阶段、CNS区域和衍生物种以及其表型潜力方面不同，已经在各种SCI动物模型中进行了测试。从历史上看，在SCI领域，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。然而，少得多的注意力已经面向在受损的脊髓中靶向星形胶质细胞功能障碍，尽管星形胶质细胞在正常的CNS功能和患病的神经系统中发挥着不可或缺的作用。尽管相对缺乏研究，但基于细胞移植的星形胶质细胞靶向可以追溯到SCI动物模型中的一些最早的移植研究。在这篇综述中，我们将描述SCI模型中涉及细胞移植靶向星形胶质细胞的工作历史。我们还将谈到该领域的现状，以及未来的重要方向，因为我们正在努力将这种方法发展成为SCI患者的可行策略。实际问题，如交货时间，移植途径和免疫抑制需求超出了本审查的范围。
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.
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