Pro-angiogenic scaffold-free Bio three-dimensional conduit developed from human induced pluripotent stem cell-derived mesenchymal stem cells promotes peripheral nerve regeneration
Pro-angiogenic scaffold-free Bio three-dimensional conduit developed from human induced pluripotent stem cell-derived mesenchymal stem cells promotes peripheral nerve regeneration
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DOI：
10.1038/s41598-020-68745-1
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发表时间：
2020-07-21
影响因子：
4.6
通讯作者：
Ikeya, Makoto
中科院分区：
文献类型：
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作者：
Mitsuzawa, Sadaki;Zhao, Chengzhu;Ikeya, Makoto
虽然自体神经移植被广泛接受为治疗节段性神经缺损的金标准，但自体神经的采集具有高度侵入性，并导致切除部分的功能丧失。对此，已有人工材料制作的人工神经导管的报道，但其神经再生的效果仍有待提高。本研究旨在探讨由人诱导多能干细胞来源的间充质干细胞（iMSCs）组成的生物三维（3D）导管的疗效和机制。用Bio - 3D导管或硅胶管桥接免疫缺陷大鼠坐骨神经5mm神经间隙。术后8周评估功能和组织学恢复情况。基于形态学、运动学、电生理学和湿肌重量，Bio 3D组的再生神经明显优于硅胶组。基因表达分析显示神经营养因子和血管生成因子。肉眼观察显示，生物三维导管内部和表面均有新生血管形成。经皮下植入后，iMSCs可诱导血管生成。利用间充质干细胞制备生物三维神经导管是一种有效的动物神经再生策略。这项技术将在未来的临床应用中发挥重要作用。
Although autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects, harvesting autologous nerves is highly invasive and leads to functional loss of the ablated part. In response, artificial nerve conduits made of artificial materials have been reported, but the efficacy of the nerve regeneration still needs improvement. The purpose of this study is to investigate the efficacy and mechanism of the Bio three-dimensional (3D) conduit composed of xeno-free human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs). The 5-mm nerve gap of the sciatic nerve in immunodeficient rats was bridged with the Bio 3D conduit or silicone tube. Functional and histological recovery were assessed at 8 weeks after surgery. The regenerated nerve in the Bio 3D group was significantly superior to that in the silicone group based on morphology, kinematics, electrophysiology, and wet muscle weight. Gene expression analyses demonstrated neurotrophic and angiogenic factors. Macroscopic observation revealed neovascularization both inside and on the surface of the Bio 3D conduit. Upon their subcutaneous implantation, iMSCs could induce angiogenesis. The Bio 3D conduit fabricated from iMSCs are an effective strategy for nerve regeneration in animal model. This technology will be useful in future clinical situations.