Different cell cycle responses of wound healing protagonists to transient in vitro hypoxia.

Polyploidization is a process present in cells of many different human tissues. Since it is also prominent in human wound healing in vivo and in vitro, we focused on the influence of hypoxia on the cells' proliferation and polyploidization response. The proliferation response of two major cell types, involved in human wound healing, human dermal microvascular endothelial cells (HDMEC) and normal human dermal fibroblasts (NHDF) was quite similar in the in vitro setup: proliferation significantly decreased under the influence of 18 h of hypoxia and was reinitiated after 72 h of reoxygenation. The cells' response concerning their tendency towards the development of polyploidy was different: NHDF did not generate any polyploid cells, which stands in contrast to former in vitro studies with human wound-derived fibroblasts, but HDMEC were characterized by the presence of both mononuclear and binuclear tetraploid cells. The number of tetraploids was downregulated during hypoxia and increased during reoxygenation, accompanied by proliferation onset. The immunomicroscopic survey of HDMEC opened up a cell cycle model, which might be useful in the future to evaluate cell cycle modulations leading to polyploidy without the need to apply any additional cell cycle inhibitors.