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2018 ; 9
(27
): 19328-19341
Nephropedia Template TP
gab.com Text
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Stress and stem cells: adult Muse cells tolerate extensive genotoxic stimuli
better than mesenchymal stromal cells
#MMPMID29721206
Alessio N
; Squillaro T
; Özcan S
; Di Bernardo G
; Venditti M
; Melone M
; Peluso G
; Galderisi U
Oncotarget
2018[Apr]; 9
(27
): 19328-19341
PMID29721206
show ga
Mesenchymal stromal cells (MSCs) are not a homogenous population but comprehend
several cell types, such as stem cells, progenitor cells, fibroblasts, and other
types of cells. Among these is a population of pluripotent stem cells, which
represent around 1-3% of MSCs. These cells, named multilineage-differentiating
stress enduring (Muse) cells, are stress-tolerant cells. Stem cells may undergo
several rounds of intrinsic and extrinsic stresses due to their long life and
must have a robust and effective DNA damage checkpoint and DNA repair mechanism,
which, following a genotoxic episode, promote the complete recovery of cells
rather than triggering senescence and/or apoptosis. We evaluated how Muse cells
can cope with DNA damaging stress in comparison with MSCs. We found that Muse
cells were resistant to chemical and physical genotoxic stresses better than
non-Muse cells. Indeed, the level of senescence and apoptosis was lower in Muse
cells. Our results proved that the DNA damage repair system (DDR) was properly
activated following injury in Muse cells. While in non-Muse cells some anomalies
may have occurred because, in some cases, the activation of the DDR persisted by
48 hr post damage, in others no activation took place. In Muse cells, the
non-homologous end joining (NHEJ) enzymatic activity increases compared to other
cells, while single-strand repair activity (NER, BER) does not. In conclusion,
the high ability of Muse cells to cope with genotoxic stress is related to their
quick and efficient sensing of DNA damage and activation of DNA repair systems.