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Mimicking Cardiac Fibrosis in a Dish: Fibroblast Density Rather than Collagen Density Weakens Cardiomyocyte Function
- Source :
- Journal of Cardiovascular Translational Research, 10(2), 116-127. Springer, Journal of Cardiovascular Translational Research, 10(2), 116-127, Journal of Cardiovascular Translational Research
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Cardiac fibrosis is one of the most devastating effects of cardiac disease. Current in vitro models of cardiac fibrosis do not sufficiently mimic the complex in vivo environment of the cardiomyocyte. We determined the local composition and mechanical properties of the myocardium in established mouse models of genetic and acquired fibrosis and tested the effect of myocardial composition on cardiomyocyte contractility in vitro by systematically manipulating the number of fibroblasts and collagen concentration in a platform of engineered cardiac microtissues. The in vitro results showed that while increasing collagen content had little effect on microtissue contraction, increasing fibroblast density caused a significant reduction in contraction force. In addition, the beating frequency dropped significantly in tissues consisting of 50% cardiac fibroblasts or higher. Despite apparent dissimilarities between native and in vitro fibrosis, the latter allows for the independent analysis of local determinants of fibrosis, which is not possible in vivo. Electronic supplementary material The online version of this article (doi:10.1007/s12265-017-9737-1) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Contraction (grammar)
Cardiac fibrosis
Pharmaceutical Science
Cell Communication
Cardiac fibroblast proliferation
Contractility
03 medical and health sciences
Heart Rate
Fibrosis
In vivo
ECM accumulation
Internal medicine
Engineered cardiac tissue
Genetics
medicine
Animals
Genetics(clinical)
Myocytes, Cardiac
Fibroblast
Cells, Cultured
Genetics (clinical)
Cell Proliferation
Chemistry
Fibroblasts
medicine.disease
Myocardial Contraction
Coculture Techniques
In vitro
Extracellular Matrix
Cardiomyocyte functionality
Cell biology
Muscular Dystrophy, Duchenne
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Mice, Inbred mdx
cardiovascular system
Cardiology
Molecular Medicine
Original Article
Collagen
Cardiomyopathies
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 19375395 and 19375387
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of Cardiovascular Translational Research
- Accession number :
- edsair.doi.dedup.....bbb5ea8ed055d69bb3356a3ed2cb0253