ArticlePloS one2015
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 151 citations in OpenAlex.
- Establishment and longitudinal characterisation of a feeder-free embryonic stem-like cell line (ATES1) derived from blastomeres of the climbing perch, Anabas testudineus.Fish physiology and biochemistry · 2026Article
- Building a human pluripotent stem cell-based gonadal niche: improving in vitro systems with in vivo insights.Human reproduction update · 2025Review
- Yolk Sac Elements in Tumors Derived from Pluripotent Stem Cells: Borrowing Knowledge from Human Germ Cell Tumors.International journal of molecular sciences · 2025Review
- Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior.Advanced biology · 2025Article
- The clinical landscape of CAR NK cells.Experimental hematology & oncology · 2025Review
- Development of Standardized Methods and Analytical Tools.Advances in experimental medicine and biology · 2025Review
- Review
- Robust bioprocess design and evaluation of commercial media for the serial expansion of human induced pluripotent stem cell aggregate cultures in vertical-wheel bioreactors.Stem cell research & therapy · 2024Article
- Canine induced pluripotent stem cells can be successfully maintained in weekend-free culture systems.The Journal of veterinary medical science · 2024Article
- Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity.Cellular and molecular life sciences : CMLS · 2024Article
- Gains of 20q11.21 in human pluripotent stem cells: Insights from cancer research.Stem cell reports · 2024Review
- 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
- Overcoming the Variability of iPSCs in the Manufacturing of Cell-Based Therapies.International journal of molecular sciences · 2023Review
- Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis.Stem cell research & therapy · 2023Article
- Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters.Journal of extracellular biology · 2023Article
- More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome.Science advances · 2023Article
- A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems.Cell discovery · 2023Article
- Semi-automated optimized method to isolate CRISPR/Cas9 edited human pluripotent stem cell clones.Stem cell research & therapy · 2023Article
- DUSP6 is a memory retention feedback regulator of ERK signaling for cellular resilience of human pluripotent stem cells in response to dissociation.Scientific reports · 2023Article
- Serial Cultivation of an MSC-Like Cell Line with Enzyme-Free Passaging Using a Microporous Titanium Scaffold.Materials (Basel, Switzerland) · 2023Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them a promising source of material for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a combinatorial study on both hESCs and hiPSCs to compare the effects of enzymatic vs. mechanical passaging, and feeder-free vs. mouse embryonic fibroblast feeder substrate, on the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. In extensive experiments involving over 100 continuous passages, we observed that both enzymatic passaging and feeder-free culture were associated with genetic instability, higher rates of cell proliferation, and persistence of OCT4/POU5F1-positive cells in teratomas, with enzymatic passaging having the stronger effect. In all combinations of culture conditions except for mechanical passaging on feeder layers, we noted recurrent deletions in the genomic region containing the tumor suppressor gene TP53, which was associated with decreased mRNA expression of TP53, as well as alterations in the expression of several downstream genes consistent with a decrease in the activity of the TP53 pathway. Among the hESC cultures, we also observed culture-associated variations in global gene expression and DNA methylation. The effects of enzymatic passaging and feeder-free conditions were also observed in hiPSC cultures. Our results highlight the need for careful assessment of the effects of culture conditions on cells intended for clinical therapies.
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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.