@Article{,
AUTHOR = {Séverine Froget, Emmanuelle Barthelemy, François Guillot, Christophe Soler, Marie-Claude Coudert, Marc Benbunan, Christine Dosquet},
TITLE = {Wound healing mediator production by human dermal fibroblasts grown within a collagen-GAG matrix for skin repair in humans},
JOURNAL = {European Cytokine Network},
VOLUME = {14},
YEAR = {2003},
NUMBER = {1},
PAGES = {60--64},
URL = {http://www.techscience.com/ECN/v14n1/66553},
ISSN = {1952-4005},
ABSTRACT = {Cell and tissue therapy applications in humans are being used increasingly, particularly for tissue
repair. Several reconstructed skin models have been proposed. Wound healing involves overlapping steps of
inflammation, cell migration and proliferation, neovascularisation, extracellular matrix production and remo-delling.
This is regulated by numerous cytokines and other soluble mediators. We have prepared dermal
substitutes (DS) consisting of a collagen-GAG, three-dimensional matrix colonized by human dermal fibroblasts
(HDF), isolated by skin explant or enzymatic digestion of the skin for potential therapeutic use in humans. To test
the functionality of these DS, we measured (ELISA) the stimulatory effect on HDF in the matrix, of serial dilutions
of human serum (HS) on the production of wound healing mediators: interleukin-8 (IL-8), vascular endothelial
growth factor (VEGF), keratinocyte growth factor (KGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1).
We observed: 1) a stimulatory effect of HS on HDF production of the different mediators tested, with a
dose-dependent effect in the case of IL-8 and VEGF. 2) A matrix-potentiating effect on the production of the
different mediators by HDF. 3) A decrease in the production of IL-8 and VEGF when HDF isolated by enzymatic
digestion was used to colonize the matrix as compared with HDF isolated by skin explant. We conclude: 1) that
the production by HDF, in a collagen-GAG matrix, of mediators involved in cutaneous wound healing is decreased
when HDF are isolated by enzymatic skin digestion rather than by skin explant. 2) That measurement of the
production of cytokines or other mediators could be a useful quality control to test the functionality of
tissue-engineered DS for tissue repair therapy in humans and more generally of cells prepared for cell therapy.},
DOI = {}
}