Methods for the maturation of cardiomyocytes on amniotic fluid cell-derived ECM, cellular constructs, and uses for cardiotoxicity and proarrhythmic screening of drug compounds

A method for determining the cardiotoxicity or proarrhythmic effect of a drug compound in vitro, the method comprising:

• (i) obtaining immature cardiomyocytes derived from human induced pluripotent stem cells, wherein the immature cardiomyocytes exhibit a single nucleus;
• (ii) contacting the immature cardiomyocytes with an extracellular matrix obtained from culturing isolated cells from amniotic fluid obtained from a human at greater than 37 weeks of gestational age (AFC-ECM), wherein the AFC-ECM comprises laminin, collagen alpha-1 (XVIII), basement membrane-specific heparan sulfate proteoglycan core protein, agrin, vimentin, and collagen alpha-2 (IV), or isoforms thereof;
• (iii) culturing the immature cardiomyocytes with the AFC-ECM in a culture media to form a layer of mature cardiomyocytes on the AFC-ECM, wherein the mature cardiomyocytes exhibit two nuclei;
• and
• (iv) contacting the drug compound with mature cardiomyocytes and observing for a change in the electrophysiology of the mature cardiomyocytes to confirm whether the drug compound has a cardiotoxic or proarrhythmic effect on the mature cardiomyocytes.