Rehabilitative Training Enhances Therapeutic Effect of Human-iPSC-Derived Neural Stem/Progenitor Cells Transplantation in Chronic Spinal Cord Injury

Takahiro Shibata, Syoichi Tashiro, Shinsuke Shibata, Munehisa Shinozaki, Tomoko Shindo, Shogo Hashimoto, Momotaro Kawai, Takahiro Kitagawa, Kentaro Ago, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)83-96
Number of pages14
JournalStem Cells Translational Medicine
Volume12
Issue number2
DOIs
Publication statusPublished - 2023 Mar 3

Keywords

  • cell transplantation
  • chronic spinal cord injury
  • combination treatment
  • human-induced pluripotent stem cell-derived neural stem/progenitor cells
  • rehabilitative training

ASJC Scopus subject areas

  • General Medicine

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