Oxidized cfDNA up-regulates NRF2 and PPARG2 and reduces ROS production in MSCs. These effects should be taken into account when considering therapeutic applications of stem cells.

GC-rich sequences present in cfDNA stimulate endogenous stems cells when body is exposed to adverse conditions. GC-rich fragments of human DNA may be used for preconditioning of therapeutic MSCs aiming at an increase in their survival in the ailing body.

Human mesenchymal stem cells (MSCs) are widely used in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activ ity within the organism still remain unanswered. In lesion regions the level of cell death increases and DNA fragments from dead cells (cell free DNA, cfDNA) are accumulated in blood. We have shown that in vitro contact of adipose derived MSCs with cfDNA fragments the increase of transcription activity (evaluated by the increase of total cellular RNA and rRNA) is observed. GC rich cfDNA fragments (GC DNA) activated the TLR9 dependent signal pathway causing up regulation of expression of TLR9 and MyD88, the TLR9 signaling pathway adapter. AT rich DNA fragments did not increase the TLR9 expression, but did increase the level of MyD88 mRNA. So we suggest that AT DNA acts via some other receptors, which, nevertheless, activate MyD88 dependent signalling in MSCs. We have also shown that cfDNA fragments decreased the activity of caspase, an apoptotic enzyme. Thus, cfDNA can significantly influence the functional activity of MSC by activating the TLR9 and MyD88 dependent signal pathways and by lowering the apoptosis level.