Research on elimination of heterogenity of iPS cells that is believed to be causative in the tumor formation.

已知诱导多能干细胞具有分化成各种类型的细胞和在体外无限增殖的能力。然而，iPS细胞的这些特性在分化为免疫活性细胞后常常诱导肿瘤形成和针对宿主细胞的刺激性免疫反应。因此，“自杀基因”的参与是确保iPS细胞在再生医学应用中的安全性的先决条件。我们的新型自杀基因方法利用人胸苷酸激酶（tmpk）基因与无毒前药叠氮胸苷（AZT）的组合，叠氮胸苷（AZT）转化为毒性代谢产物AZT-三磷酸，导致诱导细胞死亡。我们选择了仅表达未分化iPS细胞的tmpk基因的CR 4启动子，以通过在AZT施用后去除分化细胞簇中残留的未分化细胞来确保使用分化iPS细胞的安全性。我们已经在体外验证了我们的方法的有效性。

Induced pluripotent stem cells are known to possess ability to differentiate into various types of cells and to proliferate infinitely in vitro. Whereas, these characters of iPS cells often induce tumor formation and irritable immune reactions against the host cells following differentiate into immunocompetent cells. Thus, involvement of "suicide genes" is prerequisite to reserve safety of iPS cells in the application of regenerative medicine. Our novel suicide gene approach utilizes a gene for human thymidylate kinase (tmpk) in combination with a non-toxic prodrug, azido-thymidine (AZT) which is converted into toxic metabolites, AZT-triphosphate that leads to induce cell death. We chose the CR4 promoter for tmpk gene that expresses only undifferentiated iPS cells to ensure the safety of usage of differentiated iPS cells by removing residual undifferentiated cells in the differentiated cell cluster after AZT-administration. We have validated effectiveness of our approach in vitro.