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

抄録

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 rejection, 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.