Transplantation of Human iPS Cell-Derived Neural Cells with an Artificial Nerve Conduit Leads to Cellular Retention in the Transplanted Area and Improves Motor Function in a Mouse Spinal Cord Injury Model
Transplantation of Human iPS Cell-Derived Neural Cells with an Artificial Nerve Conduit Leads to Cellular Retention in the Transplanted Area and Improves Motor Function in a Mouse Spinal Cord Injury Model
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DOI：
10.17264/stmarieng.10.27
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发表时间：
2019
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通讯作者：
Ken Tomochika;N. Arimitsu;Masanori A. Murayama;C. Hirotsu;Kazufumi Nagata;K. Takai;J. Shimizu;Tsutomu Akazawa;Yoshiaki Torii;Tasuku Umehara;M. Iinuma;H. Niki;N. Suzuki
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作者：
Ken Tomochika;N. Arimitsu;Masanori A. Murayama;C. Hirotsu;Kazufumi Nagata;K. Takai;J. Shimizu;Tsutomu Akazawa;Yoshiaki Torii;Tasuku Umehara;M. Iinuma;H. Niki;N. Suzuki
脊髓损伤（SCI）引起运动功能障碍。诱导多能细胞（iPSCs）正在成为一种新的细胞来源，可用于移植治疗，而无需担心伦理问题或免疫排斥，但一种最有效的临床移植策略仍有待开发。人类iPSCs （hiPSCs）满足了移植细胞的要求，而Nerbridge是一种由聚羟基乙酸（PGA）和胶原制成的导管，已被用作移植细胞的支架，并在临床上用于周围神经的再生。该支架不仅适用于周围神经损伤，也适用于中枢神经损伤。我们进行了一项实验研究，我们将hipsc与Nerbridge结合，并将细胞移植到小鼠SCI模型中，我们通过在Th11处完全横切创建了该模型。将细胞移植到损伤部位。带神经导管的神经干/祖细胞（NSPCs）移植比单个NSPCs悬液移植或不带NSPCs的神经导管移植更有效地改善了运动功能。组织学分析显示，移植细胞中表达人核抗原的比例很高，损伤部位神经丝m阳性轴突的比例很高。我们的研究结果表明，NSPCs和神经导管的联合应用具有治疗脊髓损伤的潜力。
Spinal cord injury (SCI) causes motor dysfunction. Induced pluripotent cells (iPSCs) are becoming a new source for cells that can be used in transplantation therapy without concern for ethical issues or immune rejec‐ tion, but an optimally effective clinical strategy for transplantation remains to be developed. Human iPSCs (hiPSCs) satisfy the requirement for grafted cells, and Nerbridge, a conduit made of polyglycolic acid (PGA) and collagen, has been used as a scaffold for grafted cells and employed clinically for regeneration of peripheral nerves. This scaffold may be applicable not only for peripheral nerve injury but also for central nervous system injury. We conducted an experimental study in which we combined hiPSCs with Nerbridge and transplanted the cells into a murine SCI model, which we created by complete transection at Th11. Cells were transplanted into the injury site. Transplantation of neural stem/progenitor cells (NSPCs) with the nerve conduit improved motor function more effectively than did transplantation of a single cell suspension of NSPCs or implantation of a nerve conduit without NSPCs. Histologic analyses revealed a high percentage of transplanted cells expressing human nuclear antigen and a high percentage of neurofilament M-positive axons at the site of injury. Our results suggest that the combined application of NSPCs and a nerve conduit has potential as treatment for SCI.