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Engineered human cardiac tissues for modeling heart diseases

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Heart disease is one of the major life-threatening diseases withhigh mortality and incidence worldwide. Several model systems,such as primary cells and animals, have been used to understandheart diseases and establish appropriate treatments. However,they have limitations in accuracy and reproducibility inrecapitulating disease pathophysiology and evaluating drug responses. In recent years, three-dimensional (3D) cardiac tissuemodels produced using tissue engineering technology and humancells have outperformed conventional models. In particular,the integration of cell reprogramming techniques with bioengineeringplatforms (e.g., microfluidics, scaffolds, bioprinting, andbiophysical stimuli) has facilitated the development of heart-ona-chip, cardiac spheroid/organoid, and engineered heart tissue(EHT) to recapitulate the structural and functional features ofthe native human heart. These cardiac models have improvedheart disease modeling and toxicological evaluation. In this review,we summarize the cell types for the fabrication of cardiactissue models, introduce diverse 3D human cardiac tissue models,and discuss the strategies to enhance their complexity and maturity. Finally, recent studies in the modeling of various heartdiseases are reviewed.

Abstract

Heart disease is one of the major life-threatening diseases withhigh mortality and incidence worldwide. Several model systems,such as primary cells and animals, have been used to understandheart diseases and establish appropriate treatments. However,they have limitations in accuracy and reproducibility inrecapitulating disease pathophysiology and evaluating drug responses. In recent years, three-dimensional (3D) cardiac tissuemodels produced using tissue engineering technology and humancells have outperformed conventional models. In particular,the integration of cell reprogramming techniques with bioengineeringplatforms (e.g., microfluidics, scaffolds, bioprinting, andbiophysical stimuli) has facilitated the development of heart-ona-chip, cardiac spheroid/organoid, and engineered heart tissue(EHT) to recapitulate the structural and functional features ofthe native human heart. These cardiac models have improvedheart disease modeling and toxicological evaluation. In this review,we summarize the cell types for the fabrication of cardiactissue models, introduce diverse 3D human cardiac tissue models,and discuss the strategies to enhance their complexity and maturity. Finally, recent studies in the modeling of various heartdiseases are reviewed.

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