title: Adipose tissue-derived stromal cells inhibit TGF-β1-induced differentiation of human dermal fibroblasts and keloid scar-derived fibroblasts in a paracrine fashion.
abstract: BACKGROUND
  Adipose tissue-derived stromal cells augment wound healing and skin regeneration. It is unknown whether and how they can also influence dermal scarring. The authors hypothesized that adipose tissue-derived stromal cells inhibit adverse differentiation of dermal fibroblasts induced by the pivotal factor in scarring, namely, transforming growth factor (TGF)-β.
  
  
  METHODS
  TGF-β1-treated adult human dermal fibroblasts and keloid scar-derived fibroblasts were incubated with adipose tissue-derived stromal cell-conditioned medium and assessed for proliferation and differentiation, particularly the production of collagen, expression of SM22α, and development of hypertrophy and contractility.
  
  
  RESULTS
  TGF-β1-induced proliferation of adult human dermal fibroblasts was abolished by adipose tissue-derived stromal cell-conditioned medium. Simultaneously, the medium reduced SM22α gene and protein expression of TGF-β1-treated adult human dermal fibroblasts, and their contractility was reduced also. Furthermore, the medium strongly reduced transcription of collagen I and III genes and their corresponding proteins. In contrast, it tipped the balance of matrix turnover to degradation through stimulating gene expression of matrix metalloproteinase (MMP)-1, MMP-2, and MMP-14, whereas MMP-2 activity was up-regulated also. Even in end-stage myofibroblasts (i.e., keloid scar-derived fibroblasts), adipose tissue-derived stromal cell-conditioned medium suppressed TGF-β1-induced myofibroblast contraction and collagen III gene expression.
  
  
  CONCLUSIONS
  The authors show that adipose tissue-derived stromal cells inhibit TGF-β1-induced adverse differentiation and function of adult human dermal fibroblasts and TGF-β1-induced contraction in keloid scar-derived fibroblasts, in a paracrine fashion.
authors.affiliation: Groningen, Amsterdam, Heerenveen, and Zwolle, The Netherlands From the Departments of Pathology and Medical Biology and Plastic Surgery, University Medical Centre Groningen, University of Groningen; the Department of Dermatology, VU University Medical Center; and Bergman Clinics Heerenveen and Zwolle.
authors.forename: Maroesjka
authors.initials: M
authors.lastname: Spiekman
authors.forename: Ewa
authors.initials: E
authors.lastname: Przybyt
authors.forename: Josée A
authors.initials: JA
authors.lastname: Plantinga
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
authors.forename: Berend
authors.initials: B
authors.lastname: van der Lei
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation; D017439:Cicatrix, Hypertrophic / Q000473:pathology*; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D007627:Keloid / Q000473:pathology*; D019899:Paracrine Communication; D017154:Stromal Cells / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D053773:Transforming Growth Factor beta1