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. Conclusion: 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.