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Bao, X. ; Wang, J. ; Zhou, G.* ; Aszodi, A.* ; Schönitzer, V.* ; Scherthan, H.* ; Atkinson, M.J. ; Rosemann, M.

Extended in vitro culture of primary human mesenchymal stem cells downregulates Brca1-related genes and impairs DNA double-strand break recognition.

FEBS Open Bio 10, 1238-1250 (2020)
Publ. Version/Full Text Postprint DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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 (gamma-H2AX + 53BP1 foci) and repair (pBRCA1 + gamma-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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brca1 ; Cellular Aging ; Dna Repair ; Homologous Recombination ; Mesenchymal Stem Cells; Stromal Cells; Abc Transporters; Bone-marrow; Therapy; Resistant; Senescence; Expression; Autophagy; Pattern
ISSN (print) / ISBN 2211-5463
Journal FEBS Open Bio
Quellenangaben Volume: 10, Issue: 7, Pages: 1238-1250 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)