Induced pluripotent stem (iPS) cells can be established via forced epigenetic reprogramming of various somatic cells and selection based on given criteria. Human iPS cells are preferred for clinical applications because they present fewer ethical concerns than embryonic stem cells. However, technical issues of stability and safety must be fully validated before clinical use. Moreover, heart regenerative therapies would require approximately 10(9) cardiomyocytes per person, necessitating the following technical considerations: (1) genetically and epigenetically stable scaling up of the iPS cells, (2) efficient and reproducible differentiation, and (3) highly reliable cell purification. Furthermore, (4) strategies for efficient iPS transplantation, rapid maturation, and functional integration of grafted cardiomyocytes into the host myocardium are critical unmet technologies. Herein, we discuss current progress and unmet problems for the realization of heart regenerative therapy.
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