ArticleStem cells translational medicine2019
Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy.
Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- Development of evolutionarily conserved viral integration sites as safe harbors for human gene therapy.iScience · 2025Article
- Molecular imaging of stem cell therapies in ischemic stroke.European journal of nuclear medicine and molecular imaging · 2025Review
- CRISPR-COPIES: an in silico platform for discovery of neutral integration sites for CRISPR/Cas-facilitated gene integration.Nucleic acids research · 2024Article
- Combining the induced pluripotent stem cell (iPSC) technology with chimeric antigen receptor (CAR)-based immunotherapy: recent advances, challenges, and future prospects.Frontiers in cell and developmental biology · 2024Review
- Therapeutic effects against high-grade glioblastoma mediated by engineered induced neural stem cells combined with GD2-specific CAR-NK.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies.Biomarker research · 2023Review
- Integrating Omics and CRISPR Technology for Identification and Verification of Genomic Safe Harbor Loci in the Chicken Genome.Biological procedures online · 2023Article
- Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification.Frontiers in cell and developmental biology · 2023Article
- Genomics and epigenetics guided identification of tissue-specific genomic safe harbors.Genome biology · 2022Article
- Tumorigenicity risk of iPSCsPrecision clinical medicine · 2022Review
- Emerging Therapeutic Strategies for Parkinson's Disease and Future Prospects: A 2021 Update.Biomedicines · 2022Review
- Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates.Nature medicine · 2022Article
- Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes.Transplant international : official journal of the European Society for Organ Transplantation · 2022Review
- Hematopoietic stem cell- and induced pluripotent stem cell-derived CAR-NK cells as reliable cell-based therapy solutions.Stem cells translational medicine · 2021Review
- Targeting theMolecular therapy. Methods & clinical development · 2021Article
- Novel cell sources for bone regeneration.MedComm · 2021Review
- Fluorescence-based actin turnover dynamics of stem cells as a profiling method for stem cell functional evolution, heterogeneity and phenotypic lineage parsing.Methods (San Diego, Calif.) · 2021Article
- Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells.Stem cells translational medicine · 2020Article
- Cell-Based Therapeutic Approaches for Cystic Fibrosis.International journal of molecular sciences · 2020Review
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of human induced pluripotent stem cells (hiPSCs) and recent advances in cell engineering have opened new prospects for cell-based therapy. However, there are concerns that must be addressed prior to their broad clinical applications and a major concern is tumorigenicity. Suicide gene approaches could eliminate wayward tumor-initiating cells even after cell transplantation, but their efficacy remains controversial. Another concern is the safety of genome editing. Our knowledge of human genomic safe harbors (GSHs) is still insufficient, making it difficult to predict the influence of gene integration on nearby genes. Here, we showed the topological architecture of human GSH candidates, AAVS1, CCR5, human ROSA26, and an extragenic GSH locus on chromosome 1 (Chr1-eGSH). Chr1-eGSH permitted robust transgene expression, but a 2 Mb-distant gene within the same topologically associated domain showed aberrant expression. Although knockin iPSCs carrying the suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were sufficiently sensitive to ganciclovir in vitro, the resulting teratomas showed varying degrees of resistance to the drug in vivo. Our findings suggest that the Chr1-eGSH is not suitable for therapeutic gene integration and highlight that topological analysis could facilitate exploration of human GSHs for regenerative medicine applications. Our data indicate that the HSV-TK/ganciclovir suicide gene approach alone may be not an adequate safeguard against the risk of teratoma, and suggest that the combination of several distinct approaches could reduce the risks associated with cell therapy. Stem Cells Translational Medicine 2019;8:627&638.
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