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Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation
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 inju...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577910/ https://www.ncbi.nlm.nih.gov/pubmed/37845736 http://dx.doi.org/10.1186/s41232-023-00298-y |
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author | Suematsu, Yu Nagoshi, Narihito Shinozaki, Munehisa Kase, Yoshitaka Saijo, Yusuke Hashimoto, Shogo Shibata, Takahiro Kajikawa, Keita Kamata, Yasuhiro Ozaki, Masahiro Yasutake, Kaori Shindo, Tomoko Shibata, Shinsuke Matsumoto, Morio Nakamura, Masaya Okano, Hideyuki |
author_facet | Suematsu, Yu Nagoshi, Narihito Shinozaki, Munehisa Kase, Yoshitaka Saijo, Yusuke Hashimoto, Shogo Shibata, Takahiro Kajikawa, Keita Kamata, Yasuhiro Ozaki, Masahiro Yasutake, Kaori Shindo, Tomoko Shibata, Shinsuke Matsumoto, Morio Nakamura, Masaya Okano, Hideyuki |
author_sort | Suematsu, Yu |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41232-023-00298-y. |
format | Online Article Text |
id | pubmed-10577910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105779102023-10-17 Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation Suematsu, Yu Nagoshi, Narihito Shinozaki, Munehisa Kase, Yoshitaka Saijo, Yusuke Hashimoto, Shogo Shibata, Takahiro Kajikawa, Keita Kamata, Yasuhiro Ozaki, Masahiro Yasutake, Kaori Shindo, Tomoko Shibata, Shinsuke Matsumoto, Morio Nakamura, Masaya Okano, Hideyuki Inflamm Regen Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41232-023-00298-y. BioMed Central 2023-10-16 /pmc/articles/PMC10577910/ /pubmed/37845736 http://dx.doi.org/10.1186/s41232-023-00298-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Suematsu, Yu Nagoshi, Narihito Shinozaki, Munehisa Kase, Yoshitaka Saijo, Yusuke Hashimoto, Shogo Shibata, Takahiro Kajikawa, Keita Kamata, Yasuhiro Ozaki, Masahiro Yasutake, Kaori Shindo, Tomoko Shibata, Shinsuke Matsumoto, Morio Nakamura, Masaya Okano, Hideyuki Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation |
title | Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation |
title_full | Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation |
title_fullStr | Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation |
title_full_unstemmed | Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation |
title_short | Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation |
title_sort | hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human ipsc-derived neural stem/progenitor cell transplantation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577910/ https://www.ncbi.nlm.nih.gov/pubmed/37845736 http://dx.doi.org/10.1186/s41232-023-00298-y |
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