Universität zu Köln

Heras-Bautista, Carlos O., Mikhael, Nelly, Lam, Jennifer, Shinde, Vaibhav, Katsen-Globa, Alisa, Dieluweit, Sabine, Molcanyi, Marek, Uvarov, Vladimir, Juetten, Peter, Sahito, Raja G. A., Mederos-Henry, Francisco, Piechot, Alexander, Brockmeier, Konrad, Hescheler, Juergen, Sachinidis, Agapios and Pfannkuche, Kurt (2019). Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts. Acta Biomater., 89. S. 180 - 193. OXFORD: ELSEVIER SCI LTD. ISSN 1878-7568

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Abstract

Pathophysiological conditions, such as myocardial infarction and mechanical overload affect the mammalian heart integrity, leading to a stiffened fibrotic tissue. With respect to the pathophysiology of cardiac fibrosis but also in the limelight of upcoming approaches of cardiac cell therapy it is of interest to decipher the interaction of cardiomyocytes with fibrotic matrix. Therefore, we designed a hydrogel-based model to engineer fibrotic tissue in vitro as an approach to predict the behavior of cardiomyocytes facing increased matrix rigidity. Here, we generated pure induced pluripotent stem cell-derived cardiomyocytes and cultured them on engineered polyacrylamide hydrogels matching the elasticities of healthy as well as fibrotic cardiac tissue. Only in cardiomyocytes cultured on matrices with fibrotic-like elasticity, transcriptional profiling revealed a substantial up-regulation of a whole panel of cardiac fibrosis-associated transcripts, including collagen I and III, decorin, lumican, and periostin. In addition, matrix metalloproteinases and their inhibitors, known to be essential in cardiac remodeling, were found to be elevated as well as insulin-like growth factor 2. Control experiments with primary cardiac fibroblasts were analyzed and did not show comparable behavior. In conclusion, we do not only present a snapshot on the transcriptomic fingerprint alterations in cardiomyocytes under pathological conditions but also provide a new reproducible approach to study the effects of fibrotic environments to various cell types. Statement of Significance ageing population in many western countries is faced with an increasing burden of ageing-related diseases such as heart failure which is associated with cardiac fibrosis. A deeper understanding of the interaction of organotypic cells with altered extracellular matrix mechanical properties is of pivotal importance to understand the underlying mechanisms. Here, we present a strategy to combine hydrogel matrices with induced pluripotent stem cell derived cardiomyocytes to study the effect of matrix stiffening on these cells. Our findings suggest an active role of matrix stiffening on cardiomyocyte function and heart failure progression. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heras-Bautista, Carlos O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mikhael, Nelly UNSPECIFIED UNSPECIFIED UNSPECIFIED Lam, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Shinde, Vaibhav UNSPECIFIED UNSPECIFIED UNSPECIFIED Katsen-Globa, Alisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieluweit, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Molcanyi, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Uvarov, Vladimir UNSPECIFIED UNSPECIFIED UNSPECIFIED Juetten, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahito, Raja G. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mederos-Henry, Francisco UNSPECIFIED UNSPECIFIED UNSPECIFIED Piechot, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmeier, Konrad UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfannkuche, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-150705
DOI:	10.1016/j.actbio.2019.03.017
Journal or Publication Title:	Acta Biomater.
Volume:	89
Page Range:	S. 180 - 193
Date:	2019
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1878-7568
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-DERIVED CARDIOMYOCYTES; ACUTE MYOCARDIAL-INFARCTION; FACTOR HOMOLOGOUS FACTORS; ATOMIC-FORCE MICROSCOPE; SUBSTRATE STIFFNESS; CARDIAC MYOCYTES; FIBROBLASTS; ENGRAFTMENT; LUMICAN; SHAPE Multiple languages Engineering, Biomedical; Materials Science, Biomaterials Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15070