Rehabilitative Training Enhances Therapeutic Effect of Human iPSC-Derived Neural Stem/Progenitor Cells Transplantation in Chronic Spinal Cord Injury. (17th January 2023)

• Record Type: Journal Article
• Authors: Shibata, Takahiro; Tashiro, Syoichi; Shibata, Shinsuke; Shinozaki, Munehisa; Shindo, Tomoko; Hashimoto, Shogo; Kawai, Momotaro; Kitagawa, Takahiro; Ago, Kentaro; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki; Nagoshi, Narihito
• Is Part Of: Stem cells translational medicine. Volume 12:Number 2(2023)
• Page Start: 83
• Page End: 96
• Publication Date: 2023-01-17
• Subjects: chronic spinal cord injury -- human induced pluripotent stem cell-derived neural stem/progenitor cells -- cell transplantation -- rehabilitative training -- combination treatment; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1093/stcltm/szac089
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Cell transplantation therapy using human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a new therapeutic strategy for spinal cord injury (SCI). Preclinical studies have demonstrated the efficacy of hiPSC-NS/PCs transplantation in the subacute phase of SCI. However, locomotor recovery secondary to hiPSC-NS/PCs transplantation is limited in the chronic phase, suggesting that additional treatment, including rehabilitative training, is required to ensure recovery. The therapeutic potential of hiPSC-NS/PCs that qualify for clinical application is yet to be fully delineated. Therefore, in this study, we investigated the therapeutic effect of the combined therapy of clinical-grade hiPSC-NS/PCs transplantation and rehabilitative training that could produce synergistic effects in a rodent model of chronic SCI. Our findings indicated that rehabilitative training promoted the survival rate and neuronal differentiation of transplanted hiPSC-NS/PCs. The combination therapy was able to enhance the expressions of the BDNF and NT-3 proteins in the spinal cord tissue. Moreover, rehabilitation promoted neuronal activity and increased 5-HT-positive fibers at the lumbar enlargement. Consequently, the combination therapy significantly improved motor functions. The findings of this study suggest that the combined therapy of hiPSC-NS/PCs transplantation and rehabilitative training has the potential to promote functional recovery even when initiated during chronic SCI. Graphical Abstract: