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Transplanted enteric neural stem cells integrate within the developing chick spinal cord: implications for spinal cord repair

机译:移植的肠道神经干细胞集成在发育中的小鸡脊髓内:对脊髓修复的影响

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Abstract Spinal cord injury ( SCI ) causes paralysis, multisystem impairment and reduced life expectancy, as yet with no cure. Stem cell therapy can potentially replace lost neurons, promote axonal regeneration and limit scar formation, but an optimal stem cell source has yet to be found. Enteric neural stem cells ( ENSC ) isolated from the enteric nervous system ( ENS ) of the gastrointestinal ( GI ) tract are an attractive source. Here, we used the chick embryo to assess the potential of ENSC to integrate within the developing spinal cord. In vitro , isolated ENSC formed extensive cell connections when co‐cultured with spinal cord ( SC )‐derived cells. Further, qRT ‐ PCR analysis revealed the presence of TuJ1 + neurons, S100 + glia and Sox10 + stem cells within ENSC neurospheres, as well as expression of key neuronal subtype genes, at levels comparable to SC tissue. Following ENSC transplantation to an ablated region of chick embryo SC , donor neurons were found up to 12?days later. These neurons formed bridging connections within the SC injury zone, aligned along the anterior/posterior axis, and were immunopositive for TuJ1. These data provide early proof of principle support for the use of ENSC s for SCI , and encourage further research into their potential for repair.
机译:摘要脊髓损伤(SCI)导致瘫痪,多系统损害和降低的预期寿命,尚未治愈。干细胞疗法可能会替代丢失的神经元,促进轴突再生和极限瘢痕形成,但尚未找到最佳干细胞源。肠道神经干细胞(ENSC)与肠胃(GI)道的肠道神经系统(肌肉)分离是一种有吸引力的来源。在这里,我们使用Chick Embryo来评估ENSC的潜力,以在开发的脊髓内整合。在体外,当用脊髓(SC)的细胞共培养时,隔离的ENSC形成了广泛的电池连接。此外,QRT - PCR分析显示,在ESENC神经球中的TuJ1 +神经元,S100 + Glia和Sox10 +干细胞的存在,以及关键神经元亚型基因的表达,在与SC组织相比的水平。随后在EnSC移植到鸡胚胚SC的烧蚀区域后,供体神经元在12天内发现12天。这些神经元在SC损伤区内形成了桥接连接,沿着前轴排列,并为TUJ1的免疫倍数。这些数据提供了早期的原理支持证明,用于使用恩斯科SCI,并鼓励进一步研究其修复潜力。

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