Transplantation of human glial-restricted neural precursors into injured spinal cord promotes functional and sensory recovery without causing allodynia
Transplantation of human glial-restricted neural precursors into injured spinal cord promotes functional and sensory recovery without causing allodynia
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DOI：
10.3109/14653249.2010.510504
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发表时间：
2011-01-01
期刊：
影响因子：
4.5
通讯作者：
Kurpad, Shekar N.
中科院分区：
文献类型：
--
作者：
Alexanian, Arshak R.;Svendsen, Clive N.;Kurpad, Shekar N.
背景目标。中枢神经系统的创伤性损伤引起特定细胞群的损伤和变性，随后功能丧失。细胞移植是通过替换丢失或受损的细胞群来治疗这种损伤的策略。许多种细胞被认为是脊柱内移植的候选者。人神经前体细胞（human neural precursor cells，hNPC）来源于死后胎儿组织，易于分离和扩增，能够产生大量神经元和神经胶质细胞。移植到神经系统后，hNPC产生成熟的神经表型，并允许在一些神经退行性疾病模型中的功能改善。在这项研究中，我们的目的是阐明不同的神经元和神经胶质祖细胞的hNPC对脊髓损伤（SCI）大鼠的运动和感觉功能的治疗作用。方法.通过细胞分选和神经诱导从hNPC获得不同的祖细胞群，产生NCAM（+）A2 B5（+）、NCAM（+）A2 B5（-）或A2 B5（+）NG 2（+）的细胞培养物。然后通过移植到SCI大鼠中，测试这些不同的细胞群在修复受损脊髓中的功效。结果A2 B5（+）NG 2（+）hNPC群体显著改善SCI大鼠的运动和感觉（后肢）功能恢复。重要的是，移植后在前肢中未观察到异常疼痛反应。结论.这种治疗方法可以改善SCI后的功能恢复，而不会引起异常性疼痛。进一步研究A2 B5（+）NG 2（+）细胞在损伤脊髓中存活、分化和整合的能力。
Background aims. Traumatic injuries of the central nervous system cause damage and degeneration of specific cell populations with subsequent functional loss. Cell transplantation is a strategy to treat such injuries by replacing lost or damaged cell populations. Many kinds of cells are considered candidates for intraspinal transplantation. Human neural precursor cells (hNPC) derived from post-mortem fetal tissue are easy to isolate and expand, and are capable of producing large numbers of neuronal and glial cells. After transplantation into the nervous system, hNPC produce mature neural phenotypes and permit functional improvement in some models of neurodegenerative disease. In this study, we aimed to elucidate the therapeutic effect of different neuronal and glial progenitor populations of hNPC on locomotor and sensory functions of spinal cord-injured (SCI) rats. Methods. Different populations of progenitor cells were obtained from hNPC by cell sorting and neural induction, resulting in cell cultures that were NCAM(+) A2B5(+), NCAM(+) A2B5(-) or A2B5(+) NG2(+). These different cell populations were then tested for efficacy in repair of the injured spinal cord by transplantation into rats with SCI. Results. The A2B5(+) NG2(+) population of hNPC significantly improved locomotor and sensory (hindlimb) functional recovery of SCI rats. Importantly, no abnormal pain responses were observed in the forelimbs following transplantation. Conclusions. This treatment approach can improve functional recovery after SCI without causing allodynia. Further studies will be conducted to investigate the ability of A2B5(+) NG2(+) cells to survive, differentiate and integrate in the injured spinal cord.