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Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues
We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299411/ https://www.ncbi.nlm.nih.gov/pubmed/28181589 http://dx.doi.org/10.1038/srep42290 |
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author | Liau, Brian Jackman, Christopher P. Li, Yanzhen Bursac, Nenad |
author_facet | Liau, Brian Jackman, Christopher P. Li, Yanzhen Bursac, Nenad |
author_sort | Liau, Brian |
collection | PubMed |
description | We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues. |
format | Online Article Text |
id | pubmed-5299411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52994112017-02-13 Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues Liau, Brian Jackman, Christopher P. Li, Yanzhen Bursac, Nenad Sci Rep Article We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues. Nature Publishing Group 2017-02-09 /pmc/articles/PMC5299411/ /pubmed/28181589 http://dx.doi.org/10.1038/srep42290 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Liau, Brian Jackman, Christopher P. Li, Yanzhen Bursac, Nenad Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
title | Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
title_full | Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
title_fullStr | Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
title_full_unstemmed | Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
title_short | Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
title_sort | developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299411/ https://www.ncbi.nlm.nih.gov/pubmed/28181589 http://dx.doi.org/10.1038/srep42290 |
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