Engineered Cardiac Tissues for in vitro Assessment of Contractile Function and Repair Mechanisms

Kim, Do Eun; Lee, Eun Jung; Martens, Timothy P.; Kara, Rina J.; Chaudhry, Hina W.; Itescu, Silviu; Costa, Kevin D.

doi:10.1109/iembs.2006.259753

Cited by 10 publications

(8 citation statements)

References 14 publications

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“…This level of organization observed in mouse ECT is distinctly absent from the stellate-shaped CMs commonly observed in monolayer cultures. As in other species 1–3, 29, 31, 32 , mouse CMs in the ECT responded appropriately to increasing stretch in accordance with the Frank-Starling law. Similar to observations in intact myocardial tissue 34–36 , increasing the perfusion temperature to 37°C significantly accelerated the rates of contraction and relaxation in mouse ECT.…”

Section: Discussionsupporting

confidence: 71%

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Neonatal Mouse–Derived Engineered Cardiac Tissue

Lange

Hegge

Grimes

et al. 2011

Circulation Research

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Rationale Cardiomyocytes cultured in a mechanically active three-dimensional configuration can be used for studies that correlate contractile performance to cellular physiology. Current engineered cardiac tissue (ECT) models employ cells derived from either rat or chick hearts. Development of a murine ECT would provide access to many existing models of cardiac disease, and open the possibility of performing targeted genetic manipulation with the ability to directly assess contractile and molecular variables. Objective To generate, characterize and validate mouse ECT using a physiologically relevant model of hypertrophic cardiomyopathy. Methods and Results We generated mechanically integrated ECT using isolated neonatal mouse cardiac cells derived from both wild type and myosin binding protein C (cMyBP-C) null mouse hearts. The murine ECT's produce consistent contractile forces that follow the Frank-Starling law, accept physiologic pacing. cMyBP-C null ECT show characteristic acceleration of contraction kinetics. Adenoviral-mediated expression of human cMyBP-C in murine cMyBP-C null ECT restores contractile properties to levels indistinguishable from those of wild type ECT. Importantly, the cardiomyocytes used to construct the cMyBP-C−/− ECT have yet to undergo the significant hypertrophic remodeling that occurs in vivo. Thus, this murine ECT model reveals a contractile phenotype that is specific to the genetic mutation rather than to secondary remodeling events. Conclusions Data presented here show mouse ECT to be an efficient and cost effective platform to study the primary effects of genetic manipulation on cardiac contractile function. This model provides a previously unavailable tool to study specific sarcomeric protein mutations in an intact mammalian muscle system.

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Section: Discussionsupporting

confidence: 71%

“…ECT generated from rat and chick hearts recapitulate several aspects of the contractile phenotype of intact cardiac tissue 1–3, 29, 31, 32 . We therefore examined the contractile responses of murine ECT to standard physiologic challenges.…”

Section: Resultsmentioning

confidence: 99%

Neonatal Mouse–Derived Engineered Cardiac Tissue

Lange

Hegge

Grimes

et al. 2011

Circulation Research

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“…Due to the tension generated within the tissue, the longitudinal alignment of the cardiomyocytes was observed at the outer surface of the ring tissue. This was consistent with previous reports [6–8], in which the conventional ECM-based procedures were employed for cardiac tissue fabrication. The H&E-stained section of a cardiac tissue ring after 7-day cultivation is shown in Figure 3f.…”

Section: Resultssupporting

confidence: 93%

“…Thus, significant efforts are currently focused on developing three-dimensional (3D) cardiac tissue models. The most common approach is an extracellular matrix (ECM)-based procedure in which spontaneous 3D tissue formation can be induced from a mixture of cardiomyocytes and ECM precursors such as collagen and Matrigel [6–8]. ECM components play essential roles in the development and signaling of cardiac tissues and also contribute to the enhancement of mechanical strengths with maintenance of tissue flexibility [9].…”

Section: Introductionmentioning

confidence: 99%

Construction of Cardiac Tissue Rings Using a Magnetic Tissue Fabrication Technique

Akiyama

Ito

Sato

et al. 2010

IJMS

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Here we applied a magnetic force-based tissue engineering technique to cardiac tissue fabrication. A mixture of extracellular matrix precursor and cardiomyocytes labeled with magnetic nanoparticles was added into a well containing a central polycarbonate cylinder. With the use of a magnet, the cells were attracted to the bottom of the well and allowed to form a cell layer. During cultivation, the cell layer shrank towards the cylinder, leading to the formation of a ring-shaped tissue that possessed a multilayered cell structure and contractile properties. These results indicate that magnetic tissue fabrication is a promising approach for cardiac tissue engineering.

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“…Indeed, engineered heart tissue has been created by mixing neonatal rat heart cells in a fibrin matrix, attached to flexible posts [94], and engineered three-dimensional muscle strips and cardiac organoid chambers with key characteristics of cardiac physiology have been examined to calculate the rate, force, and kinetics of the contractions [95,96]. The engineered cardiac tissue constructs are also suitable for studying the changes in CM properties upon increased exercise by mechanical stretches.…”

Section: Cardiac Tissue Bio-engineeringmentioning

confidence: 99%

Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: from the genetic, epigenetic, and tissue modeling perspectives

Chow

Boheler

2013

Stem Cell Res Ther

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Heart diseases remain a major cause of mortality and morbidity worldwide. However, terminally differentiated human adult cardiomyocytes (CMs) possess a very limited innate ability to regenerate. Directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs has enabled clinicians and researchers to pursue the novel therapeutic paradigm of cell-based cardiac regeneration. In addition to tissue engineering and transplantation studies, the need for functional CMs has also prompted researchers to explore molecular pathways and develop strategies to improve the quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this review, we describe various approaches in directed CM differentiation and driven maturation, and discuss potential limitations associated with hESCs and iPSCs, with an emphasis on the role of epigenetic regulation and chromatin remodeling, in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for drug discovery and toxicity screening, disease modeling, and clinical applications.

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Engineered Cardiac Tissues for in vitro Assessment of Contractile Function and Repair Mechanisms

Cited by 10 publications

References 14 publications

Neonatal Mouse–Derived Engineered Cardiac Tissue

Neonatal Mouse–Derived Engineered Cardiac Tissue

Construction of Cardiac Tissue Rings Using a Magnetic Tissue Fabrication Technique

Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: from the genetic, epigenetic, and tissue modeling perspectives

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