Cardiac tissue models

Author(s):  
Joycelyn K. Yip ◽  
Megan L. McCain
Keyword(s):  
2017 ◽  
Vol 131 (13) ◽  
pp. 1393-1404 ◽  
Author(s):  
Anastasia Korolj ◽  
Erika Yan Wang ◽  
Robert A. Civitarese ◽  
Milica Radisic

Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing.


2016 ◽  
Vol 96 ◽  
pp. 203-213 ◽  
Author(s):  
Anurag Mathur ◽  
Zhen Ma ◽  
Peter Loskill ◽  
Shaheen Jeeawoody ◽  
Kevin E. Healy

Author(s):  
Ariane C. C. van Spreeuwel ◽  
Noortje A. M. Bax ◽  
Jasper Foolen ◽  
M. A. Borochin ◽  
Daisy W. J. van der Schaft ◽  
...  

Engineered cardiac tissue models become increasingly important for understanding normal and disease cardiac physiology [1]. Where clinical diagnostic tools usually measure overall function of the heart, cardiac tissue models make it possible to focus on single CMs and their microenvironment. The use of in-vitro cardiac disease models can give more insight in the functionality changes of CMs during disease and thereby speed up the development of new therapies. Therefore, we aim to develop a model for healthy and diseased myocardium to study the effect of diseased microenvironments on the mechanical performance of CMs. The platform consists of 3D engineered microtissues with matrix, CMs and fibroblasts (FBs) on an array of polydimethylsiloxane (PDMS) microposts and allows for real-time characterization of CMs and their surrounding matrix. The design was adapted from Legant et. al. [2] and enables us to measure inhomogeneous tissue forces which may occur if not all cells contract equally. Here we focus on optimization and validation of the platform to measure contraction forces and gain insight in CM mechanical functioning.


Bioprinting ◽  
2019 ◽  
Vol 13 ◽  
pp. e00040 ◽  
Author(s):  
Justin Liu ◽  
Jingjin He ◽  
Jingfeng Liu ◽  
Xuanyi Ma ◽  
Qu Chen ◽  
...  

2020 ◽  
Author(s):  
Diwakar Turaga ◽  
Oriane B. Matthys ◽  
Tracy A. Hookway ◽  
David A. Joy ◽  
Meredith Calvert ◽  
...  

AbstractNative cardiac tissue is comprised of heterogeneous cell populations that work cooperatively for proper tissue function; thus, engineered tissue models have moved toward incorporating multiple cardiac cell types in an effort to recapitulate native multicellular composition and organization. Cardiac tissue models comprised of stem cell-derived cardiomyocytes require inclusion of non-myocytes to promote stable tissue formation, yet the specific contributions of the supporting non-myocyte population on the parenchymal cardiomyocytes and cardiac microtissues have yet to be fully dissected. This gap can be partly attributed to limitations in technologies able to accurately study the individual cellular structure and function that comprise intact 3D tissues. The ability to interrogate the cell-cell interactions in 3D tissue constructs has been restricted by conventional optical imaging techniques that fail to adequately penetrate multicellular microtissues with sufficient spatial resolution. Light sheet fluorescence microscopy overcomes these constraints to enable single cell-resolution structural and functional imaging of intact cardiac microtissues. Multicellular spatial distribution analysis of heterotypic cardiac cell populations revealed that cardiomyocytes and cardiac fibroblasts were randomly distributed throughout 3D microtissues. Furthermore, calcium imaging of live cardiac microtissues enabled single-cell detection of cardiomyocyte calcium activity, which showed that functional heterogeneity correlated with spatial location within the tissues. This study demonstrates that light sheet fluorescence microscopy can be utilized to determine single-cell spatial and functional interactions of multiple cell types within intact 3D engineered microtissues, thereby facilitating the determination of structure-function relationships at both tissue-level and single-cell resolution.Impact StatementThe ability to achieve single-cell resolution by advanced 3D light imaging techniques enables exquisite new investigation of multicellular analyses in native and engineered tissues. In this study, light sheet fluorescence microscopy was used to define structure-function relationships of distinct cell types in engineered cardiac microtissues by determining heterotypic cell distributions and interactions throughout the tissues as well as by assessing regional differences in calcium handing functional properties at the individual cardiomyocyte level.


Author(s):  
Robert H. Liss ◽  
Frances A. Cotton

Daunomycin, an antibiotic used in the clinical management of acute leukemia, produces a delayed, lethal cardiac toxicity. The lethality is dose and schedule dependent; histopathologic changes induced by the drug have been described in heart, lung, and kidney from hamsters in both single and multiple dose studies. Mice given a single intravenous dose of daunomycin (10 mg/kg) die 6-7 days later. Drug distribution studies indicate that the rodents excrete most of a single dose of the drug as daunomycin and metabolite within 48 hours after dosage (M. A. Asbell, personal communication).Myocardium from the ventricles of 6 moribund BDF1 mice which had received a single intravenous dose of daunomycin (10 mg/kg), and from controls dosed with physiologic saline, was fixed in glutaraldehyde and prepared for electron microscopy.


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