Activation of DNA damage response pathways in human mesenchymal stem cells exposed to cisplatin or γ-irradiation

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

“…We also noted that -H2AX level in irradiated aMSCs started to decline after 24 hours after IR, as documented in an earlier study [96]. It was shown that these mechanisms are responsible for the radiation resistance in CSC of 4T1 breast cancer cells [101] which highlight their similar function at the biological response of irradiated MSCs from adipose origin.…”

“…We found that, ATM phosphorylation in irradiated aMSCs kept slightly detectable up to 24 hours, which might explain the significantly maintained G2/M arrest that lasted up to 24 hours after IR. This finding has been hypothesized as a mechanism of IR resistance in CSC of 4T1 cells [110]; since ATM is the most proximal initiating step in signal transduction for CC regulation to allow the DNA repair in irradiated cells [95,96,106]. That might be also explained by the early up regulation of most CC regulator genes; e.g.…”

“…The application of MSCs in radiation oncology regenerative medicine (RORM) was enhanced by their efficient radiation-induced DNA repair machinery and their relative radiation resistance [91,95,96,99,159]. Such radiation resistance was mediated by many mechanisms, e.g.…”

“…These mechanisms were also shown to be responsible for the IR resistance of cancer stem cells (CSC), also known as cancer initiating cells, which have been linked to cancer disease recurrence and aggression [100][101][102][103]. These mechanisms were tested in bmMSCs in earlier studies showing that these bmMSCs are relatively radio-resistant [95,96,[104][105][106]. Do MSCs from different tissue origins behave similarly?…”

“…In addition, the surface antigen CD105 presence is important for normal cellular DNA repair [94]. Different mechanisms have been reported explaining such radio-resistance such as, cell cycle (CC) arrest (G2/M arrest) and activation of double stranded DNA (dsDNA) damage repair; namely the homologous recombination repair (HRR) and non-homologous end joining repair (NHEJR) [95][96][97][98][99]. These mechanisms were also evidenced to be responsible for the IR resistance of cancer stem cells (CSC), also known as cancer initiating cells, which have been linked to cancer disease recurrence and aggression [100][101][102][103].…”