ArticleProceedings of the National Academy of Sciences of the United States of America2013
Inhibition of pluripotent stem cell-derived teratoma formation by small molecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 245 citations in OpenAlex.
- Trial
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- Review
- Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.Stem cell reports · 2025Review
- Do human adipose stem cell-derived artificial insulin-producing cells develop tumorigenic characteristics throughout differentiation?Molecular biology reports · 2025Article
- Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson's disease.Cell stem cell · 2025Article
- Liver organoids: Current advances and future applications for hepatology.Clinical and molecular hepatology · 2025Review
- Bone Tissue Engineering: From Biomaterials to Clinical Trials.Advances in experimental medicine and biology · 2025Review
- Evaluating Strategies to Assess the Differentiation Potential of Human Pluripotent Stem Cells: A Review, Analysis and Call for Innovation.Stem cell reviews and reports · 2025Review
- Longitudinal analysis of genetic and epigenetic changes in human pluripotent stem cells in the landscape of culture-induced abnormality.Experimental & molecular medicine · 2024Article
- The Buccal Fat Pad: A Unique Human Anatomical Structure and Rich and Easily Accessible Source of Mesenchymal Stem Cells for Tissue Repair.Bioengineering (Basel, Switzerland) · 2024Review
- Real-Time, Non-Invasive Monitoring of Neuronal Differentiation Using Intein-Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell-Based Biosensors.Advanced functional materials · 2024Article
- Past, present, and future of cell replacement therapy for parkinson's disease: a novel emphasis on host immune responses.Cell research · 2024Review
- Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.Nature communications · 2024Article
- Label-Free and High-Throughput Removal of Residual Undifferentiated Cells From iPSC-Derived Spinal Cord Progenitor Cells.Stem cells translational medicine · 2024Article
- Beyond Vision: An Overview of Regenerative Medicine and Its Current Applications in Ophthalmological Care.Cells · 2024Review
- Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity.Cellular and molecular life sciences : CMLS · 2024Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
The future of safe cell-based therapy rests on overcoming teratoma/tumor formation, in particular when using human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Because the presence of a few remaining undifferentiated hPSCs can cause undesirable teratomas after transplantation, complete removal of these cells with no/minimal damage to differentiated cells is a prerequisite for clinical application of hPSC-based therapy. Having identified a unique hESC signature of pro- and antiapoptotic gene expression profile, we hypothesized that targeting hPSC-specific antiapoptotic factor(s) (i.e., survivin or Bcl10) represents an efficient strategy to selectively eliminate pluripotent cells with teratoma potential. Here we report the successful identification of small molecules that can effectively inhibit these antiapoptotic factors, leading to selective and efficient removal of pluripotent stem cells through apoptotic cell death. In particular, a single treatment of hESC-derived mixed population with chemical inhibitors of survivin (e.g., quercetin or YM155) induced selective and complete cell death of undifferentiated hPSCs. In contrast, differentiated cell types (e.g., dopamine neurons and smooth-muscle cells) derived from hPSCs survived well and maintained their functionality. We found that quercetin-induced selective cell death is caused by mitochondrial accumulation of p53 and is sufficient to prevent teratoma formation after transplantation of hESC- or hiPSC-derived cells. Taken together, these results provide the "proof of concept" that small-molecule targeting of hPSC-specific antiapoptotic pathway(s) is a viable strategy to prevent tumor formation by selectively eliminating remaining undifferentiated pluripotent cells for safe hPSC-based therapy.
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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.