title: Adipose tissue-derived mesenchymal cells support skin reepithelialization through secretion of KGF-1 and PDGF-BB: comparison with dermal fibroblasts.
abstract: Epidermal organization and homeostasis are regulated by mesenchymal influences through paracrine actions. Until today, dermal fibroblasts (DFs) are used in the "dermal" layer to support keratinocyte growth in vitro in dermal and skin substitutes. In the present work, we used human adipose tissue-derived mesenchymal cells (ADMCs) as a support of keratinocyte growth in vitro (in monolayer culture and in 3D skin cell culture models) and in vivo (mouse wound healing models) and compared our findings with those obtained using dermal fibroblasts. ADMCs induce reepithelialization during wound healing more efficiently than DFs, by enhancing keratinocyte proliferation through cell cycle progression, and migration. This effect is mediated (at least partially) by a paracrine action of KGF-1 and PDGF-BB, which are more prominently expressed in ADMCs than in DFs. Furthermore, replacement of DFs by ADMCs in the dermal compartment of organotypic skin cultures leads to an artificial epidermis resembling to that of normal skin, concerning the general histology, although with a higher expression of cytokeratins 5 and 19. In Rag1 knockout mice, ADMCs induced a more rapid reepithelialization and a more effective wound healing, compared to dermal fibroblasts. In conclusion, we provide evidence that ADMCs can serve as supportive cells for primary keratinocyte cultures. In addition, because of their abundance and the great cell yield achieved during ADMC isolation, they represent an interesting cell source, with potential aspects for clinical use.
authors.affiliation: Department of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Vassilia-Ismini
authors.initials: VI
authors.lastname: Alexaki
authors.forename: Despoina
authors.initials: D
authors.lastname: Simantiraki
authors.forename: Marianna
authors.initials: M
authors.lastname: Panayiotopoulou
authors.forename: Olga
authors.initials: O
authors.lastname: Rasouli
authors.forename: Maria
authors.initials: M
authors.lastname: Venihaki
authors.forename: Ourania
authors.initials: O
authors.lastname: Castana
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexakis
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000077214:Becaplermin; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D012867:Skin / Q000166:cytology* / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: C496453:FGF7 protein, human; D020574:Proto-Oncogene Proteins c-sis; D051523:Fibroblast Growth Factor 7; D000077214:Becaplermin