Soft tissue fibroblasts from well healing and chronic human wounds show different rates of myofibroblasts in vitro.
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.
Department of Trauma-, Hand- and Reconstructive Surgery, Saarland University, Kirrberger Strasse, Bldng. 57, 66421, Homburg, Germany.
Florian
F
Schwarz
Martina
M
Jennewein
Monika
M
Bubel
Joerg H
JH
Holstein
Tim
T
Pohlemann
Martin
M
Oberringer
D000328:Adult; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism / Q000502:physiology*; D017695:Soft Tissue Injuries / Q000473:pathology*; D014945:Wound Healing
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016222:Fibroblast Growth Factor 2; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor