Departments of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5454, USA.
Cancer Res. 2011 Jul 15;71(14):5030-9. doi: 10.1158/0008-5472.CAN-10-4402. Epub 2011 Jun 6.
Pluripotent stem cells, both human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC), can give rise to multiple cell types and hence have tremendous potential for regenerative therapies. However, the tumorigenic potential of these cells remains a great concern, as reflected in the formation of teratomas by transplanted pluripotent cells. In clinical practice, most pluripotent cells will be differentiated into useful therapeutic cell types such as neuronal, cardiac, or endothelial cells prior to human transplantation, drastically reducing their tumorigenic potential. Our work investigated the extent to which these differentiated stem cell derivatives are truly devoid of oncogenic potential. In this study, we analyzed the gene expression patterns from three sets of hiPSC- and hESC-derivatives and the corresponding primary cells, and compared their transcriptomes with those of five different types of cancer. Our analysis revealed a significant gene expression overlap of the hiPSC- and hESC-derivatives with cancer, whereas the corresponding primary cells showed minimum overlap. Real-time quantitative PCR analysis of a set of cancer-related genes (selected on the basis of rigorous functional and pathway analyses) confirmed our results. Overall, our findings suggested that pluripotent stem cell derivatives may still bear oncogenic properties even after differentiation, and additional stringent functional assays to purify these cells should be done before they can be used for regenerative therapy.
多能干细胞，包括人类胚胎干细胞（hESC）和人类诱导多能干细胞（hiPSC），可以分化为多种细胞类型，因此在再生疗法方面具有巨大的潜力。然而，这些细胞的致瘤潜能仍然是一个很大的关注点，因为移植的多能细胞会形成畸胎瘤。在临床实践中，大多数多能细胞在移植到人体之前会被分化为有用的治疗性细胞类型，如神经元、心脏或内皮细胞，这极大地降低了它们的致瘤潜能。我们的工作研究了这些分化后的干细胞衍生物在多大程度上真正没有致癌潜能。在这项研究中，我们分析了三组 hiPSC 和 hESC 衍生物及其相应的原代细胞的基因表达模式，并将它们的转录组与五种不同类型的癌症进行了比较。我们的分析表明，hiPSC 和 hESC 衍生物与癌症的基因表达有显著的重叠，而相应的原代细胞的重叠最小。基于严格的功能和途径分析，对一组与癌症相关的基因（基于功能和途径分析选择）进行实时定量 PCR 分析，进一步证实了我们的结果。总的来说，我们的研究结果表明，多能干细胞衍生物即使在分化后仍可能具有致癌特性，在将其用于再生治疗之前，应该进行额外的严格的功能检测来纯化这些细胞。
