Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PLoS One. 2011 Apr 28;6(4):e19012. doi: 10.1371/journal.pone.0019012.
Induced 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 FINDINGS: We transplanted 2 × 10(4), 2 × 10(5), or 2 × 10(6) 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/SIGNIFICANCE: Our 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.
诱导多能干细胞（iPSCs）是一种用于心脏干细胞治疗的新型候选细胞。然而，在临床应用之前，需要进一步研究其内在的致瘤性。在这项研究中，我们研究了未分化的 iPSCs 在同种异体免疫活性受体内心肌内移植后是否具有致瘤性。
方法/主要发现：我们将来自已建立的大鼠 iPSC 系 M13 的 2×10(4)、2×10(5)或 2×10(6)个细胞，通过心肌内移植到完整或梗死的同种异体免疫活性大鼠心脏内。移植持续时间为 2、4 或 6 周。苏木精-伊红染色的组织学检查证实，未分化的大鼠 iPSCs 可以在心内和心外部位产生异质性肿瘤。此外，肿瘤发生率与细胞剂量、移植持续时间以及是否存在心肌梗死无关。
结论/意义：我们的研究表明，心脏内的同种异体 iPSC 移植可能导致原位致瘤性，并且从跳动的心脏漏出的细胞是肿瘤扩散的潜在来源，这突显了评估未来用于心脏疾病的 iPSC 治疗安全性的重要性。
