O'Rourke C, Day A G E, Murray-Dunning C, Thanabalasundaram L, Cowan J, Stevanato L, Grace N, Cameron G, Drake R A L, Sinden J, Phillips J B
Department of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK.
UCL Centre for Nerve Engineering, London, UK.
Sci Rep. 2018 Feb 13;8(1):2951. doi: 10.1038/s41598-018-20927-8.
Artificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel. EngNT-CTX sheets were delivered within collagen tubes to repair a 12 mm sciatic nerve injury model in athymic nude rats. Autologous nerve grafts (autografts) and empty tubes were used for comparison. After 8 weeks functional repair was assessed using electrophysiology. Further, detailed histological and electron microscopic analysis of the repaired nerves was performed. Results indicated that EngNT-CTX supported growth of neurites and vasculature through the injury site and facilitated reinnervation of the target muscle. These findings indicate for the first time that a clinically validated allogeneic neural stem cell line can be used to construct EngNT. This provides a potential 'off the shelf' tissue engineering solution for the treatment of nerve injury, overcoming the limitations associated with nerve autografts or the reliance on autologous cells for populating repair constructs.
由治疗性细胞构建的人工组织为改善严重周围神经损伤的治疗提供了一种很有前景的方法。在本研究中，测试了使用CTX0E03（一种条件永生化的人神经干细胞系）作为构建活性人工神经修复组织的同种异体细胞来源的有效性。将CTX0E03细胞分化后与胶原蛋白结合，形成工程化神经组织（EngNT-CTX），即细胞水凝胶的稳定排列片层。将EngNT-CTX片层置于胶原管内，用于修复无胸腺裸鼠12毫米的坐骨神经损伤模型。使用自体神经移植物（自体移植）和空管作为对照。8周后，使用电生理学评估功能修复情况。此外，对修复后的神经进行了详细的组织学和电子显微镜分析。结果表明，EngNT-CTX支持神经突和血管通过损伤部位生长，并促进靶肌肉的再支配。这些发现首次表明，经过临床验证的同种异体细胞系可用于构建EngNT。这为神经损伤治疗提供了一种潜在的“现成”组织工程解决方案，克服了与神经自体移植相关的局限性或依赖自体细胞填充修复结构的问题。
