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Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts
The myocardium is a mechanically active tissue typified by anisotropy of the resident cells [cardiomyocytes (CMs) and cardiac fibroblasts (cFBs)] and the extracellular matrix (ECM). Upon ischemic injury, the anisotropic tissue is replaced by disorganized scar tissue, resulting in loss of coordinated...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AIP Publishing LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771596/ https://www.ncbi.nlm.nih.gov/pubmed/36567768 http://dx.doi.org/10.1063/5.0108914 |
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author | Mostert, Dylan Groenen, Bart Klouda, Leda Passier, Robert Goumans, Marie-Jose Kurniawan, Nicholas A. Bouten, Carlijn V. C. |
author_facet | Mostert, Dylan Groenen, Bart Klouda, Leda Passier, Robert Goumans, Marie-Jose Kurniawan, Nicholas A. Bouten, Carlijn V. C. |
author_sort | Mostert, Dylan |
collection | PubMed |
description | The myocardium is a mechanically active tissue typified by anisotropy of the resident cells [cardiomyocytes (CMs) and cardiac fibroblasts (cFBs)] and the extracellular matrix (ECM). Upon ischemic injury, the anisotropic tissue is replaced by disorganized scar tissue, resulting in loss of coordinated contraction. Efforts to re-establish tissue anisotropy in the injured myocardium are hampered by a lack of understanding of how CM and/or cFB structural organization is affected by the two major physical cues inherent in the myocardium: ECM organization and cyclic mechanical strain. Herein, we investigate the singular and combined effect of ECM (dis)organization and cyclic strain in a two-dimensional human in vitro co-culture model of the myocardial microenvironment. We show that (an)isotropic ECM protein patterning can guide the orientation of CMs and cFBs, both in mono- and co-culture. Subsequent application of uniaxial cyclic strain—mimicking the local anisotropic deformation of beating myocardium—causes no effect when applied parallel to the anisotropic ECM. However, when cultured on isotropic substrates, cFBs, but not CMs, orient away from the direction of cyclic uniaxial strain (strain avoidance). In contrast, CMs show strain avoidance via active remodeling of their sarcomeres only when co-cultured with at least 30% cFBs. Paracrine signaling or N-cadherin-mediated communication between CMs and cFBs was no contributing factor. Our findings suggest that the mechanoresponsive cFBs provide structural guidance for CM orientation and elongation. Our study, therefore, highlights a synergistic mechanobiological interplay between CMs and cFBs in shaping tissue organization, which is of relevance for regenerating functionally organized myocardium. |
format | Online Article Text |
id | pubmed-9771596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AIP Publishing LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-97715962022-12-22 Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts Mostert, Dylan Groenen, Bart Klouda, Leda Passier, Robert Goumans, Marie-Jose Kurniawan, Nicholas A. Bouten, Carlijn V. C. APL Bioeng Articles The myocardium is a mechanically active tissue typified by anisotropy of the resident cells [cardiomyocytes (CMs) and cardiac fibroblasts (cFBs)] and the extracellular matrix (ECM). Upon ischemic injury, the anisotropic tissue is replaced by disorganized scar tissue, resulting in loss of coordinated contraction. Efforts to re-establish tissue anisotropy in the injured myocardium are hampered by a lack of understanding of how CM and/or cFB structural organization is affected by the two major physical cues inherent in the myocardium: ECM organization and cyclic mechanical strain. Herein, we investigate the singular and combined effect of ECM (dis)organization and cyclic strain in a two-dimensional human in vitro co-culture model of the myocardial microenvironment. We show that (an)isotropic ECM protein patterning can guide the orientation of CMs and cFBs, both in mono- and co-culture. Subsequent application of uniaxial cyclic strain—mimicking the local anisotropic deformation of beating myocardium—causes no effect when applied parallel to the anisotropic ECM. However, when cultured on isotropic substrates, cFBs, but not CMs, orient away from the direction of cyclic uniaxial strain (strain avoidance). In contrast, CMs show strain avoidance via active remodeling of their sarcomeres only when co-cultured with at least 30% cFBs. Paracrine signaling or N-cadherin-mediated communication between CMs and cFBs was no contributing factor. Our findings suggest that the mechanoresponsive cFBs provide structural guidance for CM orientation and elongation. Our study, therefore, highlights a synergistic mechanobiological interplay between CMs and cFBs in shaping tissue organization, which is of relevance for regenerating functionally organized myocardium. AIP Publishing LLC 2022-12-20 /pmc/articles/PMC9771596/ /pubmed/36567768 http://dx.doi.org/10.1063/5.0108914 Text en © 2022 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Articles Mostert, Dylan Groenen, Bart Klouda, Leda Passier, Robert Goumans, Marie-Jose Kurniawan, Nicholas A. Bouten, Carlijn V. C. Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
title | Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
title_full | Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
title_fullStr | Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
title_full_unstemmed | Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
title_short | Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
title_sort | human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771596/ https://www.ncbi.nlm.nih.gov/pubmed/36567768 http://dx.doi.org/10.1063/5.0108914 |
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