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.

journal_name

Plast Reconstr Surg

authors

Spiekman M,Przybyt E,Plantinga JA,Gibbs S,van der Lei B,Harmsen MC

doi

10.1097/PRS.0000000000000504

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

699-712

issue

4

eissn

0032-1052

issn

1529-4242

pii

00006534-201410000-00023

journal_volume

134

pub_type

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