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Teratomas induced by mouse embryonic stem (ES) cell transplantation

机译:小鼠胚胎干细胞移植诱导畸胎瘤

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摘要

Teratomas are tumors of mixed tridermic derivatives and are experimentally induced by embryonic stem (ES) cell transplantation. This tumorigenic potential of ES cells prevents the clinical application of ES cell research, however, the fundamental properties of teratomas remain unclear. In this study, we examined differences in teratoma formation at several transplantation sites (subcutaneous, portal vein, liver, spleen, kidney and testis) and the tumorigenic risk of varying numbers of ES cells (30; 300; 3,000; 30,000; 300,000; and 3,000,000 cells/30 μl) alone or with mouse embryonic fibroblasts (MEFs) in the testis. The subcutaneous and testis tumors grew slowly, whereas cells injected via the portal vein rapidly grew to widespread tumor formation in the liver. Liver and spleen transplantation were associated with low tumor incidence and frequent tumor formation ex situ. Undifferentiated cells characteristically proliferated in testicular teratomas, Wilms tumor-like tubular proliferation was specific in renal teratomas, and more cartilage was observed in the teratomas induced via portal vein and liver transplantation. Testicular tumor occurrence and size depended on the number of transplanted ES cells; furthermore, MEF-added transplantation increased tumor occurrence than ES cell transplantation alone. These results demonstrate the highly tumorigenic properties of ES cells; tumorigenic risk appears to depend on transplantation site as well as on the complexity of the prepared graft.
机译:畸胎瘤是混合的三聚体衍生物的肿瘤,并通过胚胎干(ES)细胞移植实验性诱导。 ES细胞的这种致癌潜力阻止了ES细胞研究的临床应用,但是,畸胎瘤的基本特性仍不清楚。在这项研究中,我们检查了几个移植部位(皮下,门静脉,肝脏,脾脏,肾脏和睾丸)畸胎瘤形成的差异以及不同数量ES细胞的致瘤风险(30; 300; 3,000; 30,000; 300,000;和3,000,000个细胞/ 30μl)单独或与睾丸中的小鼠胚胎成纤维细胞(MEF)一起使用。皮下和睾丸肿瘤生长缓慢,而经门静脉注射的细胞迅速生长,在肝脏中广泛扩散。肝和脾移植与低肿瘤发生率和异位肿瘤形成频繁相关。未分化细胞的特征是在睾丸畸胎瘤中增殖,Wilms肿瘤样肾小管增殖在肾畸胎瘤中具有特异性,并且在通过门静脉和肝移植诱导的畸胎瘤中观察到更多的软骨。睾丸肿瘤的发生和大小取决于移植的ES细胞的数量。此外,与仅ES细胞移植相比,添加MEF的移植增加了肿瘤的发生。这些结果证明了ES细胞的高度致瘤性。致瘤风险似乎取决于移植部位以及所制备移植物的复杂性。

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