Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit.
The present study focuses on the involvement of reactive oxygen species (ROS) in the process of mesenchymal stem cells "waking up" and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs), we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L-cysteine, Tempol, and Resveratrol) blocked G1-S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self-renewal.
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
O G
OG
Lyublinskaya
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
Ya G
YG
Borisov
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
N A
NA
Pugovkina
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
I S
IS
Smirnova
Department of Medical Physics, Institute of Physics, Nanotechnology and Telecommunications, Saint Petersburg State Polytechnic University, Saint Petersburg 195251, Russia.
Ju V
JV
Obidina
Department of Medical Physics, Institute of Physics, Nanotechnology and Telecommunications, Saint Petersburg State Polytechnic University, Saint Petersburg 195251, Russia.
Ju S
JS
Ivanova
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
V V
VV
Zenin
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
A N
AN
Shatrova
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
A V
AV
Borodkina
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
N D
ND
Aksenov
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
V I
VI
Zemelko
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia.
E B
EB
Burova
Federal North-West Medical Research Centre, Saint Petersburg 197341, Russia.
M V
MV
Puzanov
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia ; Department of Medical Physics, Institute of Physics, Nanotechnology and Telecommunications, Saint Petersburg State Polytechnic University, Saint Petersburg 195251, Russia.
N N
NN
Nikolsky
D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species