Adipose tissue-derived stromal cells inhibit TGF-ß1-induced differentiation of human dermal fibroblasts and keloid scar-derived fibroblasts in a paracrine fashion.

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)-ß. METHODS: TGF-ß1-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-ß1-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-ß1-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-ß1-induced myofibroblast contraction and collagen III gene expression. CONCLUSION: The authors show that adipose tissue-derived stromal cells inhibit TGF-ß1-induced adverse differentiation and function of adult human dermal fibroblasts and TGF-ß1-induced contraction in keloid scar-derived fibroblasts, in a paracrine fashion.