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Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease

The low survival rate of administered cells due to ischemic and inflammatory environments limits the efficacy of the current regenerative cell therapy in peripheral artery disease (PAD). This study aimed to develop a new method to enhance the efficacy of cell therapy in PAD using cell sheet technolo...

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Autores principales: Miyake, Keisuke, Miyagawa, Shigeru, Harada, Akima, Sawa, Yoshiki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899600/
https://www.ncbi.nlm.nih.gov/pubmed/35007760
http://dx.doi.org/10.1016/j.ymthe.2022.01.008
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author Miyake, Keisuke
Miyagawa, Shigeru
Harada, Akima
Sawa, Yoshiki
author_facet Miyake, Keisuke
Miyagawa, Shigeru
Harada, Akima
Sawa, Yoshiki
author_sort Miyake, Keisuke
collection PubMed
description The low survival rate of administered cells due to ischemic and inflammatory environments limits the efficacy of the current regenerative cell therapy in peripheral artery disease (PAD). This study aimed to develop a new method to enhance the efficacy of cell therapy in PAD using cell sheet technology. Clustered cells (CCs) from myoblast cell sheets obtained from C57/BL6 mice were administered into ischemic mouse muscles 7 days after induction of ischemia (defined as day 0). Control groups were administered with single myoblast cells (SCs) or saline. Cell survival, blood perfusion of the limb, angiogenesis, muscle regeneration, and inflammation status were evaluated. The survival of administered cells was markedly improved in CCs compared with SCs at days 7 and 28. CCs showed significantly improved blood perfusion, augmented angiogenesis with increased density of CD31(+)/α-smooth muscle actin(+) arterioles, and accelerated muscle regeneration, along with the upregulation of associated genes. Additionally, inflammation status was well regulated by CCs administration. CCs administration increased the number of macrophages and then induced polarization into an anti-inflammatory phenotype (CD11c(−)/CD206(+)), along with the increased expression of genes associated with anti-inflammatory cytokines. Our findings suggest clinical potential of rescuing severely damaged limbs in PAD using CCs.
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spelling pubmed-88996002023-03-02 Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease Miyake, Keisuke Miyagawa, Shigeru Harada, Akima Sawa, Yoshiki Mol Ther Original Article The low survival rate of administered cells due to ischemic and inflammatory environments limits the efficacy of the current regenerative cell therapy in peripheral artery disease (PAD). This study aimed to develop a new method to enhance the efficacy of cell therapy in PAD using cell sheet technology. Clustered cells (CCs) from myoblast cell sheets obtained from C57/BL6 mice were administered into ischemic mouse muscles 7 days after induction of ischemia (defined as day 0). Control groups were administered with single myoblast cells (SCs) or saline. Cell survival, blood perfusion of the limb, angiogenesis, muscle regeneration, and inflammation status were evaluated. The survival of administered cells was markedly improved in CCs compared with SCs at days 7 and 28. CCs showed significantly improved blood perfusion, augmented angiogenesis with increased density of CD31(+)/α-smooth muscle actin(+) arterioles, and accelerated muscle regeneration, along with the upregulation of associated genes. Additionally, inflammation status was well regulated by CCs administration. CCs administration increased the number of macrophages and then induced polarization into an anti-inflammatory phenotype (CD11c(−)/CD206(+)), along with the increased expression of genes associated with anti-inflammatory cytokines. Our findings suggest clinical potential of rescuing severely damaged limbs in PAD using CCs. American Society of Gene & Cell Therapy 2022-03-02 2022-01-07 /pmc/articles/PMC8899600/ /pubmed/35007760 http://dx.doi.org/10.1016/j.ymthe.2022.01.008 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Miyake, Keisuke
Miyagawa, Shigeru
Harada, Akima
Sawa, Yoshiki
Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
title Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
title_full Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
title_fullStr Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
title_full_unstemmed Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
title_short Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
title_sort engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899600/
https://www.ncbi.nlm.nih.gov/pubmed/35007760
http://dx.doi.org/10.1016/j.ymthe.2022.01.008
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