Document Detail

The influence of matrix (an)isotropy on cardiomyocyte contraction in engineered cardiac microtissues.
MedLine Citation:
PMID:  24549279     Owner:  NLM     Status:  Publisher    
In the cardiac microenvironment, cardiomyocytes (CMs) are embedded in an aligned and structured extracellular matrix (ECM) to maintain the coordinated contractile function of the heart. The cardiac fibroblast (cFB) is the main cell type responsible for producing and remodeling this matrix. In cardiac diseases, however, adverse remodeling and CM death may lead to deterioration of the aligned myocardial structure. Here, we present an in vitro cardiac model system with uniaxial and biaxial constraints to induce (an)isotropy in 3D microtissues, thereby mimicking 'healthy' aligned and 'diseased' disorganized cardiac matrices. A mixture of neonatal mouse CMs and cFBs was resuspended in a collagen-matrigel hydrogel and seeded to form microtissues to recapitulate the in vivo cellular composition. Matrix disarray led to a stellate cell shape and a disorganized sarcomere organization, while CMs in aligned matrices were more elongated and had aligned sarcomeres. Although matrix disarray has no detrimental effect on the force generated by the CMs, it did have a negative effect on the homogeneity of contraction force distribution. Furthermore, proliferation of the cFBs affected microtissue contraction as indicated by the negative correlation between the percentage of cFBs in the microtissues and their beating frequency. These results suggest that in regeneration of the diseased heart, reorganization of the disorganized matrix will contribute to recover the coordinated contraction but restoring the ratio in cellular composition (CMs and cFBs) is also a prerequisite to completely regain tissue function.
A C C van Spreeuwel; N A M Bax; A J Bastiaens; J Foolen; S Loerakker; M Borochin; D W J van der Schaft; C S Chen; F P T Baaijens; C V C Bouten
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-18
Journal Detail:
Title:  Integrative biology : quantitative biosciences from nano to macro     Volume:  -     ISSN:  1757-9708     ISO Abbreviation:  Integr Biol (Camb)     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101478378     Medline TA:  Integr Biol (Camb)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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