2015年
Conditionally replicating adenovirus prevents pluripotent stem cell-derived teratoma by specifically eliminating undifferentiated cells
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
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- 巻
- 2
- 号
- 開始ページ
- 15026
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/mtm.2015.26
- 出版者・発行元
- CELL PRESS
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.
- リンク情報
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- DOI
- https://doi.org/10.1038/mtm.2015.26
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/26269798
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533615
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000209918700038&DestApp=WOS_CPL
- URL
- http://europepmc.org/abstract/med/26269798
- URL
- http://orcid.org/0000-0003-0534-9845
- ID情報
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- DOI : 10.1038/mtm.2015.26
- ISSN : 2329-0501
- ORCIDのPut Code : 20594690
- PubMed ID : 26269798
- PubMed Central 記事ID : PMC4533615
- Web of Science ID : WOS:000209918700038