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Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia

Cell-based therapies hold great promise for the treatment of peripheral arterial disease (PAD), especially in patients presenting with severe limb ischemia, although the optimal strategy remains to be explored. In this study, we evaluated the therapeutic effect of intravenous administration of human...

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Autores principales: Hori, Yusuke, Kitani, Tomoya, Yanishi, Kenji, Suga, Takaomi, Kogure, Masaya, Kusaba, Tetsuro, Kushida, Yoshihiro, Dezawa, Mari, Matoba, Satoaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692087/
https://www.ncbi.nlm.nih.gov/pubmed/36440014
http://dx.doi.org/10.3389/fcvm.2022.981088
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author Hori, Yusuke
Kitani, Tomoya
Yanishi, Kenji
Suga, Takaomi
Kogure, Masaya
Kusaba, Tetsuro
Kushida, Yoshihiro
Dezawa, Mari
Matoba, Satoaki
author_facet Hori, Yusuke
Kitani, Tomoya
Yanishi, Kenji
Suga, Takaomi
Kogure, Masaya
Kusaba, Tetsuro
Kushida, Yoshihiro
Dezawa, Mari
Matoba, Satoaki
author_sort Hori, Yusuke
collection PubMed
description Cell-based therapies hold great promise for the treatment of peripheral arterial disease (PAD), especially in patients presenting with severe limb ischemia, although the optimal strategy remains to be explored. In this study, we evaluated the therapeutic effect of intravenous administration of human Muse cells, a unique subpopulation of mesenchymal stem cells (MSC), using a mouse model of hindlimb ischemia (HLI) without an immunosuppressant. Compared with the phosphate buffered saline (PBS) or non-Muse MSC groups, the Muse group showed significantly higher laser doppler blood flow in the ischemic limb at days 7 and 14 after HLI. Increased microvascular density [percent area of CD31(+) cells] and reduced interstitial fibrosis in the ischemic limb muscle were also observed in the Muse group. mCherry-expressing Muse cells were found in the ischemic border zone and expressed CD31 but did not in the non-ischemic limb. Muse cells produced higher amounts of vascular endothelial growth factor (VEGF) than non-Muse cells under normoxic and hypoxic conditions in vitro. In the ischemic muscle, tissue VEGF concentration and angiogenesis-related genes such as Vegfa, Angpt1, Pdgfb, and Igf1 were significantly higher in the Muse group than in the other two groups. In addition, the proportion of M2 macrophages to total macrophages and the ratio of anti-inflammatory-related genes such as IL-10, Arg1, and CD206 per iNOS were significantly higher in the Muse group than in the other two groups. In summary, Muse cells exert pleiotropic effects in a mouse model of HLI, and therefore may provide a novel therapeutic approach for the treatment of PAD patients with severe limb ischemia.
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spelling pubmed-96920872022-11-26 Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia Hori, Yusuke Kitani, Tomoya Yanishi, Kenji Suga, Takaomi Kogure, Masaya Kusaba, Tetsuro Kushida, Yoshihiro Dezawa, Mari Matoba, Satoaki Front Cardiovasc Med Cardiovascular Medicine Cell-based therapies hold great promise for the treatment of peripheral arterial disease (PAD), especially in patients presenting with severe limb ischemia, although the optimal strategy remains to be explored. In this study, we evaluated the therapeutic effect of intravenous administration of human Muse cells, a unique subpopulation of mesenchymal stem cells (MSC), using a mouse model of hindlimb ischemia (HLI) without an immunosuppressant. Compared with the phosphate buffered saline (PBS) or non-Muse MSC groups, the Muse group showed significantly higher laser doppler blood flow in the ischemic limb at days 7 and 14 after HLI. Increased microvascular density [percent area of CD31(+) cells] and reduced interstitial fibrosis in the ischemic limb muscle were also observed in the Muse group. mCherry-expressing Muse cells were found in the ischemic border zone and expressed CD31 but did not in the non-ischemic limb. Muse cells produced higher amounts of vascular endothelial growth factor (VEGF) than non-Muse cells under normoxic and hypoxic conditions in vitro. In the ischemic muscle, tissue VEGF concentration and angiogenesis-related genes such as Vegfa, Angpt1, Pdgfb, and Igf1 were significantly higher in the Muse group than in the other two groups. In addition, the proportion of M2 macrophages to total macrophages and the ratio of anti-inflammatory-related genes such as IL-10, Arg1, and CD206 per iNOS were significantly higher in the Muse group than in the other two groups. In summary, Muse cells exert pleiotropic effects in a mouse model of HLI, and therefore may provide a novel therapeutic approach for the treatment of PAD patients with severe limb ischemia. Frontiers Media S.A. 2022-11-11 /pmc/articles/PMC9692087/ /pubmed/36440014 http://dx.doi.org/10.3389/fcvm.2022.981088 Text en Copyright © 2022 Hori, Kitani, Yanishi, Suga, Kogure, Kusaba, Kushida, Dezawa and Matoba. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Hori, Yusuke
Kitani, Tomoya
Yanishi, Kenji
Suga, Takaomi
Kogure, Masaya
Kusaba, Tetsuro
Kushida, Yoshihiro
Dezawa, Mari
Matoba, Satoaki
Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia
title Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia
title_full Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia
title_fullStr Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia
title_full_unstemmed Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia
title_short Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia
title_sort intravenous administration of human muse cells recovers blood flow in a mouse model of hindlimb ischemia
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692087/
https://www.ncbi.nlm.nih.gov/pubmed/36440014
http://dx.doi.org/10.3389/fcvm.2022.981088
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