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

Inflammation and Regeneration

Research Article

Shogo Hashimoto¹  Morio Matsumoto¹  Masaya Nakamura¹  Yasuhiro Kamata¹  Narihito Nagoshi¹  Kaori Yasutake¹  Keita Kajikawa¹  Takahiro Shibata¹  Masahiro Ozaki¹  Yu Suematsu²  Yusuke Saijo²  Hideyuki Okano³  Munehisa Shinozaki³  Yoshitaka Kase⁴  Tomoko Shindo⁵  Shinsuke Shibata⁶ 

[1] Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Department of Clinical Regenerative Medicine, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutukake-Cho, Toyoake-Shi, 470-1192, Aichi, Japan;Electron Microscope Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Electron Microscope Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, 160-8582, Tokyo, Japan;Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuo-Ku, 951-8510, Niigata, Niigata, Japan;

关键词: Cell transplantation therapy;    Combination therapy;    Hepatocyte growth factor;    iPS cells;    Neural stem cells;    Neuroregeneration;    Spinal cord injury;   

DOI  :  10.1186/s41232-023-00298-y

 received in 2023-08-07, accepted in 2023-09-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHuman 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).MethodsSevere 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.ResultsThe 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.ConclusionsWe 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.

【 授权许可】

CC BY   
© Japanese Society of Inflammation and Regeneration 2023

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