In vitro modelling of disease-induced changes in the diabetic wound fibroblast
Research output: Contribution to journal › Article › peer-review
- Queen Victoria Hospital NHS Foundation Trust
- Northwick Park and St Mark's Hospital
OBJECTIVE: Fibroblasts have been shown to play an increasingly important role within diabetic wounds. While several in vitro models of diabetic wound fibroblasts have been reported, none replicate the natural progression of the disease over time, recapitulating the acquisition of the diseased phenotype. Therefore, this study aimed to establish an in vitro model of the diabetic wound fibroblast through sustained exposure of healthy dermal fibroblasts to hyperglycaemia.
METHOD: Primary human fibroblasts were isolated from discarded healthy skin tissue and were either exposed to normoglycaemic (control 5.5mM glucose) media or hyperglycaemic (25mM glucose) media for four weeks. Quantitative polymerase chain reaction was performed to measure the expression of inflammatory cytokines and chemokines.
RESULTS: In the hyperglycaemia model, stromal cell-derived factor (SDF)-1 expression remained consistently downregulated across all four weeks (p<0.01), while monocyte chemoattractant protein (MCP)-1 (p<0.001), interleukin (IL)-8 (p=0.847) and chemokine (C-X-C motif) ligand 1 (CXCL1) (p=0.872) were initially downregulated at one week followed by subsequent upregulation between 2-4 weeks.
CONCLUSION: This hyperglycaemia model may serve as a useful tool to characterise pathological changes in the diabetic wound fibroblast and help identify candidate therapeutic targets, such as SDF-1, that may reverse the pathology.
|Number of pages||4|
|Journal||Journal of Wound Care|
|Publication status||Published - 2 Apr 2021|
- Chemokines, Cytokines, Diabetes Complications, Diabetes Mellitus, Diabetic Foot/therapy, Fibroblasts, Humans, Skin/pathology, Wound Healing/physiology