Modulation of DNA glycosylase activities in mesenchymal stem cells.
Adipose-tissue derived mesenchymal stem cells (AT-MSCs) are a promising tool for use in cell-based therapies. However, in vitro expansion is required to obtain clinically relevant cell numbers, and this might increase the chance of genomic instability. DNA repair is crucial for maintaining DNA integrity. Here we have compared the initial step of base excision repair in uncultured and cultured AT-MSCs by analysis of base removal activities and expression levels of relevant DNA glycosylases. Uracil, 5-hydroxyuracil and ethenoadenine removal activities were upregulated in cultured cells compared to uncultured cells. In contrast, both the 8-oxo-7,8-dihydroguanine (8-oxoG) removal activity and the concentration of 8-oxoG bases in the DNA were reduced in the cultured cells. Gene expression analysis showed no substantial changes in mRNA expression. The glycosylase activities remained stable through at least 12 passages, suggesting that DNA repair is proficient through the period required for in vitro expansion of AT-MSCs to clinically relevant numbers.
Hildrestrand
Gunn A
GA
Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet University Hospital, Oslo, Norway.
Duggal
Shivali
S
Bjørås
Magnar
M
Luna
Luisa
L
Brinchmann
Jan E
JE
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D020869:Gene Expression Profiling; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism
C045975:5-hydroxyuracil; C024829:8-hydroxyguanine; D014498:Uracil; D006147:Guanine; D045647:DNA Glycosylases