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.

Advances in the Generation of Constructed Cardiac Tissue Derived from Induced Pluripotent Stem Cells for Disease Modeling and Therapeutic Discovery

“…Siloxanes stand out for their hydrophobicity and can function as surface substrates [26,74]. Polydimethylsiloxane (PDMS) is often used in micropatterning molds [57,58,75], biowire EHTs [74], EHT posts [2,8], and microfluidic HoCs [4,45,75,76], though there is interest in moving away from PDMS because of the absorption of hydrophobic drugs, with silicon, ceramics like glass, and thermoplastics like polymethylmethacrylate (PMMA) suggested as alternatives [45,75]. Hybrid scaffolds offer a more life-like ECM stand-in than single-polymer hydrogels, evidenced by improved tissue maturity [36].…”

“…Recapitulating native heart tissue in vitro is challenging because of the crosstalk between different cell types and the heart's unique architecture [7,57]. The heart has three layers (internal to external: endocardium, myocardium, and epicardium) that are responsible for the continuous nourishment, contraction, and maintenance of cardiac structure (Figure 1B) [31,46,58].…”

Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

“…Examples range from 2-dimensional cultures of cardiomyocytes, 98 epicardial cells, 99 and endocardial cells 100 to selforganizing organoid models with complex 3-dimensional structures. 101 Clinical implementation of stem cell-based technologies applied to the heart includes the recent development of 3-dimensional cardiac microtissues engineered from iPSCs harboring human mutations, allowing for rapid testing of potential therapeutics for correction of genetic defects and promotion of cardiac regeneration. 102,103 By guiding cell phenotypes toward desired lineages, these systems provide valuable insight into the cellular mechanisms governing human cardiac cell differentiation and development, and the use of patient-derived iPSCs is useful for understanding pathogenic mechanisms in cells with genetic signatures of disease.…”

“…Examples range from 2-dimensional cultures of cardiomyocytes, 98 epicardial cells, 99 and endocardial cells 100 to self-organizing organoid models with complex 3-dimensional structures. 101 Clinical implementation of stem cell-based technologies applied to the heart includes the recent development of 3-dimensional cardiac microtissues engineered from iPSCs harboring human mutations, allowing for rapid testing of potential therapeutics for correction of genetic defects and promotion of cardiac regeneration. 102 , 103 …”

Endothelial cell dysfunction in cardiac disease: driver or consequence?

“…This principle overlaps with the issue of perfusable vasculature discussed above. To date, no organoid culture systems have studied the inclusion of inflammatory cells, although this paradigm has been repeatedly cited as a major limitation of current organoid models and will likely be explored as perfusable systems are developed further ( Zhao et al, 2021 ; Sahara, 2023 ).…”