ArticleMolecular therapy. Methods & clinical development2016
Multiple mechanisms determine the sensitivity of human-induced pluripotent stem cells to the inducible caspase-9 safety switch.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024Review
- Tumorigenicity risk of iPSCsPrecision clinical medicine · 2022Review
- Improved safety of induced pluripotent stem cell-derived antigen-presenting cell-based cancer immunotherapy.Molecular therapy. Methods & clinical development · 2021Article
- Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells.Stem cells translational medicine · 2020Article
- A Preview of Selected Articles.Stem cells translational medicine · 2020Review
- Targeted Integration of Inducible Caspase-9 in Human iPSCs Allows EfficientInternational journal of molecular sciences · 2020Article
- Review
- Sufficiency for inducible Caspase-9 safety switch in human pluripotent stem cells and disease cells.Gene therapy · 2019Article
- Linking a cell-division gene and a suicide gene to define and improve cell therapy safety.Nature · 2018Article
- Bringing Neural Cell Therapies to the Clinic: Past and Future Strategies.Molecular therapy. Methods & clinical development · 2017Review
- Improving the safety of T-Cell therapies using an inducible caspase-9 gene.Experimental hematology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Expression of the inducible caspase-9 (iC9) suicide gene is one of the most appealing safety strategies for cell therapy and has been applied for human-induced pluripotent stem cells (hiPSC) to control the cell fate of hiPSC. iC9 can induce cell death of over 99% of iC9-transduced hiPSC (iC9-hiPSC) in less than 24 hours after exposure to chemical inducer of dimerization (CID). There is, however, a small number of resistant cells that subsequently outgrows. To ensure greater uniformity of the hiPSC response to iC9 activation, we purified a resistant population by culturing iC9-hiPSC with CID and analyzing the mechanisms by which the cells evade killing. We found that iC9-resistant hiPSC have significant heterogeneity in terms of their escape mechanisms from caspase-dependent apoptosis including reduced expression of iC9 by promoter silencing and overexpression of BCL2. As a consequence, modifying a single element alone will be insufficient to ensure sustained susceptibility of iC9 in all cells and prevent the eventual outgrowth of a resistant population. To solve this issue, we propose to isolate an iC9-sensitive population and show that this hiPSC line has sustained a uniform responsiveness to iC9-mediated growth control.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.