Systems for the Functional Evaluation of Human Heart Tissues Derived from Pluripotent Stem Cells

Abstract

Human pluripotent stem cells (hPSCs) are expected to be a promising cell source in regenerative medicine and drug discovery for the treatment of various intractable diseases. An approach for creating a 3-dimensional (3D) structure from hPSCs that mimics human cardiac tissue functions has made it theoretically possible to conduct drug discovery and cardiotoxicity tests by assessing pharmacological responses in human cardiac tissues by a screening system using a compound library. The myocardium functions as a tissue composed of organized vascular networks, supporting stromal cells and cardiac muscle cells. Considering this, the reconstruction of tissue structure by various cells of cardiovascular lineages, such as vascular cells and cardiac muscle cells, is desirable for the ideal conformation of hPSC-derived cardiac tissues. Heart-on-a-chip, an organ-on-a-chip system to evaluate the physiological pump function of 3D cardiac tissues might hold promise in medical researchs such as drug discovery and regenerative medicine. Here, we review various modalities to evaluate the function of human stem cell-derived cardiac tissues and introduce heart-on-a-chip systems that can recapitulate physiological parameters of hPSC-derived cardiac tissues.

Keywords: cardiomyocyte; cardiotoxicity; organ-on-a-chip; pluripotent stem cell.

Graphical Abstract

Figure 1.

In vitro evaluation methods for cardiotoxicity in the human heart. Abbreviations: hPSCs, human pluripotent stem cells; hPSC-CMs, cardiomyocytes induced from hPSCs; CMs, cardiomyocytes; ECs, vascular endothelial cells; MCs, vascular mural cells; 2D, 2-dimensional; 3D, three-dimensional.

Figure 2.

The application of heart-on-a-chip systems in drug discovery research and regenerative medicine. Abbreviations: 3D hPSC-CMs, three-dimensional cardiomyocytes induced from human pluripotent stem cells; 2D hPSC-CMs, 2-dimensional cardiomyocytes induced from human pluripotent stem cells.