RRC ID 45479
著者 Mitsui K, Ide K, Takayama A, Wada T, Irie R, Kosai K.
タイトル Conditionally replicating adenovirus prevents pluripotent stem cell-derived teratoma by specifically eliminating undifferentiated cells.
ジャーナル Mol Ther Methods Clin Dev
Abstract Incomplete abolition of tumorigenicity creates potential safety concerns in clinical trials of regenerative medicine based on human pluripotent stem cells (hPSCs). Here, we demonstrate that conditionally replicating adenoviruses that specifically target cancers using multiple factors (m-CRAs), originally developed as anticancer drugs, may also be useful as novel antitumorigenic agents in hPSC-based therapy. The survivin promoter was more active in undifferentiated hPSCs than the telomerase reverse transcriptase (TERT) promoter, whereas both promoters were minimally active in differentiated normal cells. Accordingly, survivin-responsive m-CRA (Surv.m-CRA) killed undifferentiated hPSCs more efficiently than TERT-responsive m-CRAs (Tert.m-CRA); both m-CRAs exhibited efficient viral replication and cytotoxicity in undifferentiated hPSCs, but not in cocultured differentiated normal cells. Pre-infection of hPSCs with Surv.m-CRA or Tert.m-CRA abolished in vivo teratoma formation in a dose-dependent manner following hPSC implantation into mice. Thus, m-CRAs, and in particular Surv.m-CRAs, represent novel antitumorigenic agents that could facilitate safe clinical applications of hPSC-based regenerative medicine.
巻・号 2
ページ 15026
公開日 2015-1-1
DOI 10.1038/mtm.2015.26
PII S2329-0501(16)30038-9
PMID 26269798
PMC PMC4533615
IF 4.533
引用数 11
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
ヒト・動物細胞 KhES-1(HES0001) 201B7(HPS0063) 253G1(HPS0002)