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

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:40

Article

Suzuki, Kota¹  Miyagawa, Shigeru¹  Liu, Li¹  Kawamura, Takuji¹  Li, Junjun¹  Qu, Xiang¹  Harada, Akima¹  Toda, Koichi¹  Yoshioka, Daisuke¹  Kainuma, Satoshi¹  Kawamura, Ai¹  Sawa, Yoshiki¹ 

[1] Osaka Univ, Dept Cardiovasc Surg, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

关键词: IPS cell;    tissue alignment;    transplantation;    ischemic cardiomyopathy;   

DOI  :  10.1016/j.healun.2021.04.010

来源: Elsevier

【 摘 要 】

BACKGROUND: 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. METHODS: 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. RESULTS: 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 hypertrophied cardiomyocytes, and an increased capillary density were also prominent in the iPS-CM group. A limited amount of engraftment of the transplanted tissue maintaining tissue alignment was observed at 2 weeks after transplantation. CONCLUSIONS: The creation of large-scale functional aligned cardiac tissue was feasible, and the transplantation of the aligned tissue improved cardiac function with angiogenesis and antifibrotic effects in a porcine cardiomyopathy model. (C) 2021 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

【 授权许可】

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