Abstract

The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation. To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs. Activation of iC9 with a specific chemical inducer of dimerization (CID) initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs. We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL) therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killing activity. iC9-expressing rejCTLs exert antitumor effects in vivo. The system efficiently and safely induces apoptosis in these rejCTLs. These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy.

Authors	Ando, Miki; Nishimura, Toshinobu; Yamazaki, Satoshi; Yamaguchi, Tomoyuki; Kawana-Tachikawa, Ai; Hayama, Tomonari; Nakauchi, Yusuke; Ando, Jun; Ota, Yasunori; Takahashi, Satoshi; Nishimura, Ken; Ohtaka, Manami; Nakanishi, M; Miles, John J.; Burrows, Scott; Brenner, Malcolm K.; Nakauchi, Hiromitsu
Journal	Stem Cell Reports
Pages	597-608
Volume	5
Date	1/10/2015
Grant ID	APP1084043
Funding Body	NHMRC
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.stemcr.2015.07.011
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