title: Differential response of human adipose tissue-derived mesenchymal stem cells, dermal fibroblasts, and keratinocytes to burn wound exudates: potential role of skin-specific chemokine CCL27.
abstract: Many cell-based regenerative medicine strategies toward tissue-engineered constructs are currently being explored. Cell-cell interactions and interactions with different biomaterials are extensively investigated, whereas very few studies address how cultured cells will interact with soluble wound-healing mediators that are present within the wound bed after transplantation. The aim of this study was to determine how adipose tissue-derived mesenchymal stem cells (ASC), dermal fibroblasts, and keratinocytes will react when they come in contact with the deep cutaneous burn wound bed. Burn wound exudates isolated from deep burn wounds were found to contain many cytokines, including chemokines and growth factors related to inflammation and wound healing. Seventeen mediators were identified by ELISA (concentration range 0.0006-9 ng/mg total protein), including the skin-specific chemokine CCL27. Burn wound exudates activated both ASC and dermal fibroblasts, but not keratinocytes, to increase secretion of CXCL1, CXCL8, CCL2, and CCL20. Notably, ASC but not fibroblasts or keratinocytes showed significant increased secretion of vascular endothelial growth factor (5-fold) and interleukin-6 (253-fold), although when the cells were incorporated in bi-layered skin substitute (SS) these differences were less pronounced. A similar discrepancy between ASC and dermal fibroblast mono-cultures was observed when recombinant human-CCL27 was used instead of burn wound exudates. Although CCL27 did not stimulate the secretion of any of the wound-healing mediators by keratinocytes, these cells, in contrast to ASC or dermal fibroblasts, showed increased proliferation and migration. Taken together, these results indicate that on transplantation, keratinocytes are primarily activated to promote wound closure. In contrast, dermal fibroblasts and, in particular, ASC respond vigorously to factors present in the wound bed, leading to increased secretion of angiogenesis/granulation tissue formation factors. Our findings have implications for the choice of cell type (ASC or dermal fibroblast) to be used in regenerative medicine strategies and indicate the importance of taking into account interactions with the wound bed when developing advanced therapies for difficult-to-close cutaneous wounds.
authors: 1 Department of Dermatology, VU University Medical Center , Amsterdam, The Netherlands .
authors: Lenie J
authors: LJ
authors: van den Broek
authors: Kim L
authors: KL
authors: Kroeze
authors: Taco
authors: T
authors: Waaijman
authors: Melanie
authors: M
authors: Breetveld
authors: Shakun C
authors: SC
authors: Sampat-Sardjoepersad
authors: Frank B
authors: FB
authors: Niessen
authors: Esther
authors: E
authors: Middelkoop
authors: Rik J
authors: RJ
authors: Scheper
authors: Susan
authors: S
authors: Gibbs
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002056:Burns / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054425:Chemokine CCL27 / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005122:Exudates and Transudates / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D014945:Wound Healing / Q000187:drug effects
chemical_list: C492276:CCL27 protein, human; D054425:Chemokine CCL27; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins
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