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Neural Stem Cell-Conditioned Medium Protects Neurons and Promotes Propriospinal Neurons Relay Neural Circuit Reconnection After Spinal Cord Injury

机译:神经干细胞条件培养基可保护神经元并促进脊髓原神经元继发脊髓损伤后中继神经回路的重新连接

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摘要

Human fetal neural stem cells (hNSCs) are used to treat a variety of neurological disorders involving spinal cord injury (SCI). Although their mechanism of action has been attributed to cell substitution, we examined the possibility that NSCs may have neuroprotective activities. The present article studied the action of hNSCs on protecting neurons and promoting corticospinal tract (CST) axon regeneration after SCI. hNSCs were isolated from the cortical tissue of spontaneously aborted human fetuses. The cells were removed from the NSC culture medium to acquire NSCM, thus excluding the effect of cell substitution. Continuous administration of the NSCM after the SCI resulted in extensive growth of the CST in the cervical region and more than tripled the formation of synaptic contacts between CST collaterals and propriospinal interneurons that project from the cervical level of the spinal cord to the lumbar level. NSCM reduced the number of caspase 3-positive apoptotic profiles at 7 days and protected against loss of the neurons 6 weeks after injury. NSCM promoted locomotor recovery with a five-point improvement on the BBB scale in adult rats. Thus, hNSCs help to set up a contour neural circuit via secretory factors, which may be the mechanism for their action in SCI rats. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
机译:人类胎儿神经干细胞(hNSC)用于治疗涉及脊髓损伤(SCI)的多种神经系统疾病。尽管它们的作用机制归因于细胞替代,但我们检查了NSC可能具有神经保护活性的可能性。本文研究了hNSCs在SCI后对保护神经元和促进皮质脊髓束(CST)轴突再生的作用。从自然流产的人类胎儿的皮质组织中分离出hNSC。从NSC培养基中除去细胞以获得NSCM,因此排除了细胞替代的影响。 SCI后连续给药NSCM导致宫颈区域CST的大量生长,并且CST侧支和脊柱椎间神经元之间的突触接触的形成增加了三倍以上,突触接触从脊髓的颈水平伸向腰水平。 NSCM在第7天减少了caspase 3阳性凋亡谱的数量,并在受伤后6周防止了神经元的丢失。 NSCM促进了成年大鼠BBB量表改善了5个方面的运动恢复。因此,hNSC通过分泌因子帮助建立轮廓神经回路,这可能是它们在SCI大鼠中起作用的机制。该手稿是国际神经修复协会(IANR)细胞移植专刊的一部分。

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