ArticleFEBS open bio2020
Extended in vitro culture of primary human mesenchymal stem cells downregulates Brca1-related genes and impairs DNA double-strand break recognition.
Article in FEBS open bio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Human adipose-derived mesenchymal stromal cells in vitro expansion for regenerative applications: tracking small genetic variants reveals dynamic changes within a genetically stable framework.Stem cell research & therapy · 2026Article
- Validation of a novel genomic biomarker of mesenchymal stem cell scalability and implications of genotype status on cellular senescence phenotypes.Scientific reports · 2026Article
- Biological and Metabolomic Characterization of Human Dermal Fibroblasts and Mesenchymal Stem Cells Derived from Human Dental Pulp and Adipose Tissue: a Pilot Comparative Study.Stem cell reviews and reports · 2025Article
- Increased DNA damage of adipose tissue-derived mesenchymal stem cells under inflammatory conditions.Heliyon · 2024Article
- Mesenchymal Stem Cell-Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?Journal of inflammation research · 2024Review
- Comparison of different gene addition strategies to modify placental derived-mesenchymal stromal cells to produce FVIII.Frontiers in immunology · 2022Article
- Psoriasis treatment using minimally manipulated umbilical cord-derived mesenchymal stem cells: A case report.World journal of clinical cases · 2021Article
- Alopecia treatment using minimally manipulated human umbilical cord-derived mesenchymal stem cells: Three case reports and review of literature.World journal of clinical cases · 2021Article
- DNA damage and repair in differentiation of stem cells and cells of connective cell lineages: A trigger or a complication?European journal of histochemistry : EJH · 2021Review
- Role ofFrontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) are multilineage adult stem cells with considerable potential for cell-based regenerative therapies. In vitro expansion changes their epigenetic and cellular properties, with a poorly understood impact on DNA damage response (DDR) and genome stability. We report here results of a transcriptome-based pathway analysis of in vitro-expanded human bone marrow-derived mesenchymal stem cell (hBM-MSCs), supplemented with cellular assays focusing on DNA double-strand break (DSB) repair. Gene pathways affected by in vitro aging were mapped using gene ontology, KEGG, and GSEA, and were found to involve DNA repair, homologous recombination (HR), cell cycle control, and chromosomal replication. Assays for the recognition (γ-H2AX + 53BP1 foci) and repair (pBRCA1 + γ-H2AX foci) of X-ray-induced DNA DSBs in hBM-MSCs show that over a period of 8 weeks of in vitro aging (i.e., about 10 doubling times), cells exhibit a reduced DDR and a higher fraction of residual DNA damage. Furthermore, a distinct subpopulation of cells with impaired DNA DSB recognition was observed. Several genes that participate in DNA repair by HR (e.g., Rad51, Rad54, BRCA1) show a 2.3- to fourfold reduction of their mRNA expression by qRT-PCR. We conclude that the in vitro expansion of hMSCs can lead to aging-related impairment of the recognition and repair of DNA breaks.
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