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Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation
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 representatio...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979489/ https://www.ncbi.nlm.nih.gov/pubmed/29584680 http://dx.doi.org/10.3390/ijms19041001 |
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author | Caley, Matthew Wall, Ivan B. Peake, Matthew Kipling, David Giles, Peter Thomas, David W. Stephens, Phil |
author_facet | Caley, Matthew Wall, Ivan B. Peake, Matthew Kipling, David Giles, Peter Thomas, David W. Stephens, Phil |
author_sort | Caley, Matthew |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5979489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59794892018-06-10 Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation Caley, Matthew Wall, Ivan B. Peake, Matthew Kipling, David Giles, Peter Thomas, David W. Stephens, Phil Int J Mol Sci Article 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. MDPI 2018-03-27 /pmc/articles/PMC5979489/ /pubmed/29584680 http://dx.doi.org/10.3390/ijms19041001 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Caley, Matthew Wall, Ivan B. Peake, Matthew Kipling, David Giles, Peter Thomas, David W. Stephens, Phil Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation |
title | Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation |
title_full | Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation |
title_fullStr | Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation |
title_full_unstemmed | Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation |
title_short | Development and Characterisation of a Human Chronic Skin Wound Cell Line—Towards an Alternative for Animal Experimentation |
title_sort | development and characterisation of a human chronic skin wound cell line—towards an alternative for animal experimentation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979489/ https://www.ncbi.nlm.nih.gov/pubmed/29584680 http://dx.doi.org/10.3390/ijms19041001 |
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