Theranostics 2022; 12(6):2758-2772. doi:10.7150/thno.67661 This issue Cite
1. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
2. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
3. Division of Cardiology, Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
4. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
5. Karis Bio Inc., Seoul, Republic of Korea
* Equal contributions
The advent of human pluripotent stem cells (hPSCs) presented a new paradigm to employ hPSC-derived cardiomyocytes (hPSC-CMs) in drug screening and disease modeling. However, hPSC-CMs differentiated in conventional two-dimensional systems are structurally and functionally immature. Moreover, these differentiation systems generate predominantly one type of cell. Since the heart includes not only CMs but other cell types, such monolayer cultures have limitations in simulating the native heart. Accordingly, three-dimensional (3D) cardiac tissues have been developed as a better platform by including various cardiac cell types and extracellular matrices. Two advances were made for 3D cardiac tissue generation. One type is engineered heart tissues (EHTs), which are constructed by 3D cell culture of cardiac cells using an engineering technology. This system provides a convenient real-time analysis of cardiac function, as well as a precise control of the input/output flow and mechanical/electrical stimulation. The other type is cardiac organoids, which are formed through self-organization of differentiating cardiac lineage cells from hPSCs. While mature cardiac organoids are more desirable, at present only primitive forms of organoids are available. In this review, we discuss various models of hEHTs and cardiac organoids emulating the human heart, focusing on their unique features, utility, and limitations.
Keywords: Human Pluripotent Stem Cell, Engineered Heart Tissue, Organoid, Disease Modeling, Drug Screening