Monocytes co-cultured with reconstructed keloid and normal skin models skew towards M2 macrophage phenotype.
Grace C LimandjajaTaco WaaijmanSanne RoffelFrank B NiessenSusan GibbsPublished in: Archives of dermatological research (2019)
Several abnormalities have been reported in the peripheral blood mononuclear cells of keloid-forming patients and particularly in the monocyte cell fraction. The goal of this in vitro study was to determine whether monocytes from keloid-prone patients contribute to the keloid phenotype in early developing keloids, and whether monocyte differentiation is affected by the keloid microenvironment. Therefore, keloid-derived keratinocytes and fibroblasts were used to reconstruct a full thickness, human, in vitro keloid scar model. The reconstructed keloid was co-cultured with monocytes from keloid-forming patients and compared to reconstructed normal skin co-cultured with monocytes from non-keloid-formers. The reconstructed keloid showed increased contraction, dermal thickness (trend) and α-SMA+ staining, but co-culture with monocytes did not further enhance the keloid phenotype. After 2-week culture, all monocytes switched from a CD11chigh/CD14high/CD68low to a CD11chigh/CD14low/CD68high phenotype. However, only monocytes co-cultured with either reconstructed keloid scar or normal skin models skewed towards the more fibrotic M2-macrophage phenotype. There was negligible fibroblast and fibrocyte differentiation in mono- and co-cultured monocytes. These results indicate that monocytes differentiate into M2 macrophages when in the vicinity of early regenerating and repairing tissue, independent of whether the individual is prone to normal or keloid scar formation.
Keyphrases
- dendritic cells
- endothelial cells
- end stage renal disease
- peripheral blood
- wound healing
- newly diagnosed
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- soft tissue
- adipose tissue
- immune response
- clinical trial
- cell therapy
- patient reported
- systemic sclerosis
- extracellular matrix
- idiopathic pulmonary fibrosis
- smooth muscle