Therapeutic efficacy of large aligned cardiac tissue derived from induced pluripotent stem cell in a porcine ischemic cardiomyopathy model.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Kota SuzukiYoshiki Sawa

Abstract

Although induced pluripotent stem (iPS) cell-derived cardiac constructs may have a potential in cardiomyogenesis of a distressed myocardium, obtaining polarity in cardiac constructs, such as via myocyte alignment, may be crucial to achieve a maximum contractile force for better clinical outcomes. We herein hypothesized that transplantation of an aligned cardiac tissue derived from iPS cells has therapeutic effects in a porcine ischemic cardiomyopathy model as a preclinical trial. Aligned cardiac tissues were developed by culturing high-purity iPS cell-derived cardiomyocytes in xeno-free conditions and transplanting them into infarct porcine hearts (iPS-CM group, n = 7; control, n = 6). Three months after treatment, therapeutic efficacy was evaluated functionally and histologically. In vitro assessment revealed that the aligned cardiac tissue containing high purity cardiomyocytes contracted homogeneously and had excellent mechanical properties. In the in vivo study, the left ventricular ejection fraction of the iPS-CM group was significantly greater than that of the control group, 3 months after transplantation (37.8% ± 2.3% vs 28.3% ± 2.5%, p < 0.05). Pathologically, attenuated interstitial fibrosis, attenuation of hypertrophie...Continue Reading

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