Nano-structural analysis of engrafted human induced pluripotent stem cell-derived cardiomyocytes in mouse hearts using a genetic-probe APEX2.

Using APEX2, an engineered peroxidase, as an imaging tag, we successfully located iPSC-derived cardiomyocytes (iPSC-CMs) engrafted in post-myocardial infarction mouse hearts for more than 6 months. APEX2 caused clear contrast in X-ray microscopy and electron microscopy, and relatively well organized sarcomere structures were formed in iPSC-CMs. Electron microscopic tomography further found the development of T-tubules and dyads in APEX2-labelled cells, which are the signature characteristics of the maturation of cardiomyocytes. APEX2 iPSCs, N=4 APEX2 iPSC-derived day7 cardiomyocytes sorted for EGFP, N=4 APEX2 iPSC-derived day14 cardiomyocytes sorted for EGFP, N=4 APEX2 iPSC-derived day21 cardiomyocytes sorted for EGFP, N=4 Control iPSCs, N=4 Control iPSC-derived day7 cardiomyocytes sorted for EGFP, N=4 Control iPSC-derived day14 cardiomyocytes sorted for EGFP, N=4 Control iPSC-derived day21 cardiomyocytes sorted for EGFP, N=4