Characterization of Maturity Marker Cardiac Troponin I in Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

Abstract

The use of human-induced pluripotent stem cells (hiPSCs) have opened new possibilities when it comes to medical discovery and patient care. One avenue that has benefitted is the cardiovascular field. Attempts to increase patient life after a cardiovascular event have led to increasingly better results as time has gone on. Yet, one issue that arises is the maturity level of hiPSC-derived cardiac myocytes (hiPSC-CMs). Current guidelines state the importance of being 100% certain that the cell type in question has fully differentiated into another, meaning that they should contain the same phenotype, markers and function as the wildtype cells in question. Cardiac myocytes have thus been difficult to consider mature due to the lack of certain maturity markers available. In this study, the irreversible, stoichiometric isoform switch between cardiac troponin I (cTnI) and slow-skeletal troponin I (ssTnI) is used to increase cTnI expression levels in the hiPSC-CMs. Promising results were found in all cases, with the adenovirus transduction of cTnI and the transfection of antisense oligonucleotides (ASOs) yielding increased or decreased cTnI expression in hiPSC-CMs. This lays the framework for further experimentation to analyze cardiac myocyte maturity via the cTnI marker.