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.

Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.

Due to an increasing life expectancy in western countries, chronic wound treatment will be an emerging challenge in the next decades. Because therapies are improving slowly appropriate diagnostic tools enabling the early prediction of the healing success remain to be developed. We used a well-established in vitro assay in combination with the analysis of 27 cytokines to discriminate between fibroblasts from chronic (n = 6) and well healing (n = 8) human wounds. Proliferation and migration of the cells as well as their response to hypoxia and their behaviour in co-culture with microvascular endothelial cells were analyzed. Myofibroblast differentiation, a time-limited essential process of regular wound healing, was also quantified. Besides weaker proliferation and migration significantly higher rates of myofibroblasts were detected in chronic wounds. With respect to the cytokine release, there was a clear trend within the group of chronic wound fibroblasts, which were releasing interferon-γ, monocyte chemotactic protein-1, granulocyte-macrophage colony stimulating factor and basic fibroblast growth factor in higher amounts than fibroblasts from healing wounds. Although the overall response of both groups of fibroblasts to hypoxia and to the contact with endothelial cells was similar, especially chronic wound fibroblasts seemed to benefit from the endothelial interaction during hypoxia and displayed better migration characteristics. The study shows (1) that the assay can identify specific features of fibroblasts derived from different human wounds and (2) that wound fibroblasts are varying in their response to the chosen parameters. Thus, current therapeutic approaches and individual healing prediction might benefit from this assay.

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