Transplantation of human iPS cell-derived oligodendrocyte precursor cells enriched neural stem/progenitor cells in chronic and subacute spinal cord injury

Society for Neuroscience Chicago 2015

Poster 226. Spinal Cord Injury: Restorative Strategies Location: Hall A Time: Sunday, October 18, 2015, 1:00 PM – 5:00 PM Program#/Poster#: 226.21/H31
Topic: C.10. Trauma

Title: Transplantation of human iPS cell-derived oligodendrocyte precursor cells enriched neural stem/progenitor cells in chronic and subacute spinal cord injury

Authors: *S. KAWABATA1, A. IWANAMI2, J. KOHYAMA3, M. TAKANO2, Y. NUMASAWA4, G. ITAKURA2, Y. KOBAYASHI2, S. SHIBATA3, H. OKANO3, M. MATSUMOTO2, M. NAKAMURA2; 1Dept. of Orthopaedics Surgery, Sch. of Medicine, Keio Univ., Shinjuku-Ku, Tokyo, Japan; 2Dept. of Orthopaedics Surgery, Sch. of Medicine, Keio Univ., Tokyo, Japan; 3Dept. of Physiology, Sch. of Medicine, Keio Univ., Tokyo, Japan; 4Dept. of Pediatrics, Sch. of Medicine, Keio Univ., Tokyo, Japan

Abstract: Background: We have reported that there are limits to functional recovery by transplantation of neural stem/progenitor cells (NS/PCs) for chronic SCI. It was partly because of inadequate remyelination of surviving axons by transplanted cells. It is well known that remyelination of demyelinated axons could be a viable target in transplantation therapy for chronic SCI. Since human iPS cell-derived oligodendrocyte precursor cells (hiPSC-OPCs) enriched NS/PCs have potentials to differentiate into mature oligodendrocytes, these cells might be effective for the chronic SCI by remyelinating demyelinated axons in the injured spinal cord. In this study, we verified the effectiveness of transplanted hiPS-OPC enriched NS/PCs for mouse chronic SCI, then compared with the subacute transplantation. Methods: hiPSC-OPCs enriched NS/PCs were induced from pre-evaluated safe iPS cell line, and cytokine antibody array experiments were performed. Contusive SCI was induced in immunodeficiency mice and these cells were transplanted into the injured spinal cord 9 or 45 days after SCI (subacute and chronic transplantation group). Instead of cells, PBS was injected in each vehicle control group. For histological analyses, mice were intracardially perfused 12 weeks after transplantation. Locomotive motor functions were periodically assessed.

Results: Cytokine antibody array analysis revealed that much more trophic factors were secreted from hiPSC-OPCs enriched NS/PCs than hiPSC-NS/PCs. Many grafted cells differentiated into MBP positive mature oligodendrocytes in both transplantation groups. Nodes of Ranvier were observed in the transplanted cells derived myelin sheathes. Furthermore transplanted cells promoted axonal growth and contributed to the synapse formation between grafted cells derived neurons and host neurons. Therefore there were many NF-H+ neuronal fibers in the both transplanted groups whereas a few NF-H+ axons were observed in the control group. The subacute transplantation group demonstrated significantly larger myelinated areas compared to control group, whereas myelinated areas did not significantly differ between the chronic transplantation group and chronic control group. Moreover, no significant motor function recovery was observed in the chronic transplantation group, compared to PBS group. Conclusion: The effectiveness of hiPSCOPC enriched NS/PCs transplantation for chronic SCI was restricted compared to the transplantation for subacute SCI. Combination therapy of transplantation with debridement of glial scar formation or rehabilitation may be critical to achieve functional recovery for chronic SCI.

Disclosures: S. Kawabata: None. A. iwanami: None. J. Kohyama: None. M. Takano: None. Y. Numasawa: None. G. Itakura: None. Y. Kobayashi: None. S. Shibata: None. H. Okano: None. M. Matsumoto: None. M. Nakamura: None.

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