Recent Advances in Generation of In Vitro Cardiac Organoids

Abstract

Cardiac organoids are in vitro self-organizing and three-dimensional structures composed of multiple cardiac cells (i.e., cardiomyocytes, endothelial cells, cardiac fibroblasts, etc.) with or without biological scaffolds. Since cardiac organoids recapitulate structural and functional characteristics of the native heart to a higher degree compared to the conventional two-dimensional culture systems, their applications, in combination with pluripotent stem cell technologies, are being widely expanded for the investigation of cardiogenesis, cardiac disease modeling, drug screening and development, and regenerative medicine. In this mini-review, recent advances in cardiac organoid technologies are summarized in chronological order, with a focus on the methodological points for each organoid formation. Further, the current limitations and the future perspectives in these promising systems are also discussed.

Keywords: biotechnology; cardiac organoid; cardiac tissue engineering; cardiogenesis; disease modeling; drug screening; pluripotent stem cell; regenerative medicine.

Figure 1

Schema of construction and applications of human cardiac organoids. (Left) Following aggregation or directed differentiation of hPSCs, cardiac organoids are constructed by differentiation and self-organization of aggregated hPSCs (i.e., EBs), or direct assembly of hPSC-derived cardiac cells such as CMs, ECs and CFBs under the 3D environment with anti-adherent culture plates, dynamic culture (shaking), and/or biological scaffolds. (Right) The applications of cardiac organoids involve the modeling of cardiogenesis and/or heart diseases, drug screening and development with or without targeting personalized medicine, and regenerative medicine. CFB, cardiac fibroblast; CM, cardiomyocyte; EB, embryoid body; EC, endothelial cell; hPSC, human pluripotent stem cell.