Abstract
Background: Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives: To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results: Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions: These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening.
Highlights
Chronic skin wounds are an ever-increasing burden to health care providers
Patient-matched fibroblast strains were isolated from the chronic venous leg ulcer wound bed and healthy, uninjured dermis of three patients as reported previously [22]
Establishment of Immortalized Chronic Wound and Patient-Matched normal fibroblasts (NFs) hTERT immortalised fibroblast cell lines were generated from chronic wound and patient matched normal fibroblast cell strains
Summary
Chronic skin wounds are an ever-increasing burden to health care providers. In the United States (US) alone between 2.4 and 4.5 million individuals suffer from chronic wounds with associated treatment costs of $10 s billions [1,2,3]. In an attempt to study chronic wound biology and to test for potentially efficacious treatments the scientific community has turned to the utilisation of chronic wound animal model systems. To generate such animal model systems the conditions that are associated with formation of the chronic wound are often artificial and ineffective. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. Human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds Such cells strains have a limited replicative lifespan and a limited reproducibility/usefulness. Conclusions: These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening
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