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Conclusions From a Meta‐Analysis: Oversimplification or Warranting Critical Analysis? Comment on the Article by Tektonidou et al

Larcher F, Garc ıa E, Garc ıa M, Escamez MJ, et al. Human plasma as a dermal scaffold for the generation of a completely autologous bioengineered skin. Transplantation 2004;77:350–5). Third, we used another approach to address this issue. The dermal equivalent of the grafted bioengineered skin was prepared with human green fluorescent protein (GFP)– positive fibroblasts. Twenty weeks after grafting we recovered dermal GFP-positive cells from grafts by collagenase treatment. Of the recovered cells, .30% were GFP positive. Obviously, the collagenase treatment releasing the GFP-positive fibroblasts yielded many other stromal cells from the host, including endothelial cells, macrophages, and mesenchymal cells (Figures 1B and C). Fourth, collagen messenger RNAs (mRNAs) measured throughout the study were amplified with primers corresponding to the human sequences. Under these conditions, mouse collagen mRNAs were not amplified. With regard to the reversibility of fibrosis in the skin graft, we think that this is an important issue. Fibrosis is not permanent, and a continuous stimulus is necessary for the establishment of the fibrotic phenotype. At present, we have no evidence that murine cells contribute to the final fibrotic phenotype, and this may be an interesting idea to test experimentally by double labeling. In conclusion, we wish to thank Ms Henrot and colleagues for the comments on the system we have used. We believe that anti-PDGFR agonistic antibodies represent one of the soluble factors that induce the fibrotic phenotype. Indeed, the loss of skin fibrosis in our mouse model some weeks after intradermal injection of anti-PDGFR antibody highlights a novel aspect of fibrosis: the establishment and the maintenance of the phenotype can be dissociated experimentally.