Cardiac applications of second harmonic generation (SHG) microscopy

摘要

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an unlimited ex vivo supply ofheart cells for cardiac applications. The establishment of pure iPSC-CMs populations is crucial for downstream medicalapplications such as human disease modeling, patient-specific stem cell therapy, human transplantation, and drugdevelopment. However, a significant challenge is the lack of an established purification method to isolate populations ofiPSC-CMs by their phenotype, maturity, and subtype due to the lack of specific iPSC-CM markers. The ability toremove potentially teratoma forming pluripotent stem cells, arrhythmia inducing immature and pacemaking cells, andother non-CMs is extremely important for engineering tissues with desired cell compositions that are both safe forhuman transplantation and that can accurately replicate cardiac functions. Contemporary purification techniques haveeither low specificity or require genetic modification. We have proposed that second harmonic generation (SHG) signals,which are known to originate from the sarcomeric myosin filaments in cardiomyocytes, can be a highly specific, labelfreemarker for identifying iPSC-CMs. Here, we demonstrate the use of SHG microscopy for characterizing iPSC-CMsand their subtypes.