Development and characterisation of a human chronic skin wound cell line - towards an alternative for animal experimentation

Caley, Matthew, Wall, Ivan, Peake, Matthew, Kipling, David, Giles, Peter ORCID: https://orcid.org/0000-0003-3143-6854, Thomas, David and Stephens, Phil ORCID: https://orcid.org/0000-0002-0840-4996 2018. Development and characterisation of a human chronic skin wound cell line - towards an alternative for animal experimentation. International Journal of Molecular Sciences 19 (4) , 1001. 10.3390/ijms19041001

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Abstract

ckground: 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Medicine
Publisher:	MDPI
ISSN:	1422-0067
Funders:	NC3Rs
Date of First Compliant Deposit:	9 April 2018
Date of Acceptance:	23 March 2018
Last Modified:	06 Nov 2024 22:21
URI:	https://orca.cardiff.ac.uk/id/eprint/110582

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