Abstract: Induced pluripotent stem cell (iPSC) refers to reprogrammed somatic cells with some specific induction methods. The most common induction method is transmitting embryonic stem cell (ESC)-related transfactors into somatic cell, to activate endogenous pluripotent genes. Up to now, except transgene technology, some small molecular substances or proteins can also realize somatic reprogram. iPSC is remarkably similar to ESC in morphology, epigenetics and differentiation ability. Because the resources of iPSC are ordinary somatic cells, iPSC technology avoids the defects of ESC in morals and immunological rejection. As a result, iPSC has an expansive prospect both in regenerative medicine and animal production. However, the existing problems like low efficiency and high risk are key barriers which limit its development. Low-efficiency greatly increases the difficulty to achieve enough iPSC, it’s time and cost-consuming. While the high-risk blocks its application in regenerative medicine and transgenic animal. These are two urgent problems in iPSC which need to be solved by researchers. A most efficient but also a high-risky method was described in this review-improving iPSC generation by restraining somatic cell senescence. This method can remarkably improve iPSC generation efficiency, while it’s also high-risk. The locus, genes and protein factors such as Ink4a/Arf, p53, pRB and p21 in charge of eliminating injured cells in body, promote cell senescence and apoptosis to prevent cancerization, which compose the important regulatory pathways in organism. Recent studies showed that silence of these genes and pathways can improve the efficiency and speed of iPSC generation, which means the generation of iPSC and tumor may use some common regulatory pathways. There are three category methods to restrain somatic cell senescence, including ameliorating iPSC culture media, employing new transgenes and regulating culture environment. Mouse iPSC generation efficiency even can be improved to 100% by this way. These results provide a new method in efficiently obtaining iPSC and researching the generation mechanism of iPSC and tumor. At the same time, this method has to face the serious security problems. iPSC is firstly reprogrammed by four canon transgenes, Oct4, Sox2, Klf4 and c-Myc, these are oncogenic transfactors in some degrees. The silence of cancer suppressor genes will improve the cancer risk of iPSC, which becomes the most serious barrier for clinical replication of this method. This paper given an outline of studies on restraining cell senescence to improve iPSC generation efficiency, including the research progress, existing defects solutions and application prospect.

Key words: iPSC, senescence, Ink4a/Arf, p53, tumor