Abstract WMP40: Tumorigenesis of Induced Pluripotent Stem Cells in Ischemic Mouse Model
Objectives: Recent studies have indicated that induced pluripotent stem (iPS) cells may provide cures for various neurological diseases. However tumorigenesis of iPS cells is serious problem which should be overcome for clinical application. In this study, we evaluated the tumorigenesis of iPS cells in a mouse model of transient middle cerebral artery occlusion (MCAO).
Methods: Adult (20-25g, 8-10 week old) male C57BL/6N mice were used. The iPS cells (5×105) were injected into the ipsilateral striatum and cortex, which were considered as the ischemic boundary zone, at 24 hour after MCAO. We used the two different murine iPS cell lines. One was established with a retrovirus introducing four transcriptional factors, c-Myc, Sox2, Oct3/4 and Klf4 (classical iPS cells). The other was established with plasmid vectors expressing above four transcriptional factors (virus-free iPS cells). Histological analysis was performed 28 days after the cell transplantation.
Results: Classical iPS cells transplanted in brain after MCAO, formed teratoma with higher probability (p <0.05) and larger volume (p <0.01) compared with those in intact brain. Among of four transcriptional factors, c-Myc, Sox2 and Oct3/4 expression were significantly increased in iPS-derived tumors in ischemic brain (p <0.01). On the other hand, virus-free iPS cells formed teratoma but there was no significant difference in tumor volume.
Conclusions: Our findings suggested that these four transcriptional factors which were integrated into the genome by retrovirus vectors, activated and promoted tumorigenesis in the ischemic brain condition. Virus-free iPS cells may be safer for transplantation therapy.
- © 2012 by American Heart Association, Inc.