Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart |
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Authors: | Zhang Yuzhen Wang Dan Chen Minglong Yang Bing Zhang Fengxiang Cao Kejiang |
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Institution: | Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. |
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Abstract: | BackgroundInduced pluripotent stem cells (iPSCs) are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients.Methodology/Principal FindingsWe transplanted 2×104, 2×105, or 2×106 cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction.Conclusions/SignificanceOur study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease. |
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