Inflammation and Regeneration (Oct 2023)

Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation

  • Yu Suematsu,
  • Narihito Nagoshi,
  • Munehisa Shinozaki,
  • Yoshitaka Kase,
  • Yusuke Saijo,
  • Shogo Hashimoto,
  • Takahiro Shibata,
  • Keita Kajikawa,
  • Yasuhiro Kamata,
  • Masahiro Ozaki,
  • Kaori Yasutake,
  • Tomoko Shindo,
  • Shinsuke Shibata,
  • Morio Matsumoto,
  • Masaya Nakamura,
  • Hideyuki Okano

DOI
https://doi.org/10.1186/s41232-023-00298-y
Journal volume & issue
Vol. 43, no. 1
pp. 1 – 17

Abstract

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Abstract Background Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI). Methods Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks. Acute-phase histological and RNA sequencing analyses were conducted. Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined. Results The acute-phase HGF-treated group exhibited vascularization, diverse anti-inflammatory effects, and activation of endogenous neural stem cells after SCI, which collectively contributed to tissue preservation. Following cell transplantation into a favorable environment, the transplanted NS/PCs survived well, facilitating remyelination and neuronal regeneration in host tissues. These comprehensive effects led to substantial enhancements in motor function in the dual-therapy group compared to the single-treatment groups. Conclusions We demonstrate that the combined therapeutic approach of HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.

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