Published online Apr 26, 2021. doi: 10.4252/wjsc.v13.i4.317
Peer-review started: February 1, 2021
First decision: February 28, 2021
Revised: March 11, 2021
Accepted: March 29, 2021
Article in press: March 29, 2021
Published online: April 26, 2021
Mesenchymal stem cells (MSCs) are in a physiologically hypoxic microenvironment in the body, while the expansion of MSCs before cell therapy is typically performed at a 20%-21% oxygen level. Thus, investigators have become increasingly aware of the effects of oxygen levels on MSCs biology and are investigating the natural niche of those cells in vitro for more detailed results.
Although some researches have focused on the effect of hypoxia on MSCs, the underlying mechanisms remain unclear. Thus, this study concentrated on the mechanism of MSC proliferation.
In this study, we aimed to explore the effect of hypoxia on the proliferation capacity of human placenta-derived MSCs (hP-MSCs) and to elucidate underlying mechanisms.
Hypoxic (2.5% oxygen) incubation was used to simulate the hypoxic microen
Hypoxic culture enhanced the proliferation capacity of hP-MSCs by modulating cell cycle progression. Western blotting assay results further confirmed that hP-MSCs cultured under hypoxia exhibited increased cyclin E1, cyclin-dependent kinase 2, and cyclin A2 expression and decreased p21 expression. In addition, CD99 expression was directly regulated by HIF-1α under hypoxia. Also, CD99-specific small interfering RNAs or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase of cell proliferation, which further confirmed the influence of HIF-1α/CD99/ERK axis on hP-MSC proliferation.
Hypoxia promoted hP-MSC proliferation in vitro in a manner dependent on the HIF-1α/CD99/ERK axis. In detail, CD99 activated pathways that transport ERK1/2 to the nucleus, resulting in increased activity of cell cycle-associated proteins.
This study contributes to the understanding of MSC biology, especially the effect of hypoxia on MSC proliferation capacity.