FIGURE 2.

Methods and functional results of maturation protocols in iPSC-CMs. Initially differentiated iPSC-CMs are known to have an immature phenotype akin to a neonatal CM. Many different maturation protocols have been developed to ensure that functional parameters and the cellular phenotype of iPSC-CMs can more closely and accurately reflect that of an adult human CM. In general, maturation protocols should aim to improve the electrophysiology, contractility, signal transduction, and metabolism of iPSC-CMs. While the combination of different maturation protocols leads to the best results of functional improvement in iPSC-CMs, it appears that culturing iPSC-CMs on soft substrates with extracellular matrix coating that is similar to the in vivo environment is imperative. ADP: action potential duration, ECM: extracellular matrix, T3: thyroid hormone T3, mTOR: mammalian target of rapamycin, ERRγ: estrogen related receptor γ, HIF1α: hypoxia inducible factor-1α. Created with www.biorender.com.