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Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration
Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracell...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5262469/ https://www.ncbi.nlm.nih.gov/pubmed/28138518 http://dx.doi.org/10.1126/sciadv.1600844 |
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author | Chen, William C. W. Wang, Zhouguang Missinato, Maria Azzurra Park, Dae Woo Long, Daniel Ward Liu, Heng-Jui Zeng, Xuemei Yates, Nathan A. Kim, Kang Wang, Yadong |
author_facet | Chen, William C. W. Wang, Zhouguang Missinato, Maria Azzurra Park, Dae Woo Long, Daniel Ward Liu, Heng-Jui Zeng, Xuemei Yates, Nathan A. Kim, Kang Wang, Yadong |
author_sort | Chen, William C. W. |
collection | PubMed |
description | Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration. |
format | Online Article Text |
id | pubmed-5262469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52624692017-01-30 Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration Chen, William C. W. Wang, Zhouguang Missinato, Maria Azzurra Park, Dae Woo Long, Daniel Ward Liu, Heng-Jui Zeng, Xuemei Yates, Nathan A. Kim, Kang Wang, Yadong Sci Adv Research Articles Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration. American Association for the Advancement of Science 2016-11-18 /pmc/articles/PMC5262469/ /pubmed/28138518 http://dx.doi.org/10.1126/sciadv.1600844 Text en Copyright © 2016, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Chen, William C. W. Wang, Zhouguang Missinato, Maria Azzurra Park, Dae Woo Long, Daniel Ward Liu, Heng-Jui Zeng, Xuemei Yates, Nathan A. Kim, Kang Wang, Yadong Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
title | Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
title_full | Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
title_fullStr | Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
title_full_unstemmed | Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
title_short | Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
title_sort | decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5262469/ https://www.ncbi.nlm.nih.gov/pubmed/28138518 http://dx.doi.org/10.1126/sciadv.1600844 |
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