Maroesjka Spiekman1, Ewa Przybyt, Josée A Plantinga, Susan Gibbs, Berend van der Lei, Martin C Harmsen. 1. 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.
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.
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.
Authors: Katharina Hoerst; Lenie van den Broek; Christoph Sachse; Oliver Klein; Uwe von Fritschen; Sue Gibbs; Sarah Hedtrich Journal: J Mol Med (Berl) Date: 2019-03-19 Impact factor: 4.599
Authors: Ryan S Chiang; Anna A Borovikova; Kassandra King; Derek A Banyard; Shadi Lalezari; Jason D Toranto; Keyianoosh Z Paydar; Garrett A Wirth; Gregory R D Evans; Alan D Widgerow Journal: Wound Repair Regen Date: 2016-05-06 Impact factor: 3.617
Authors: Maroesjka Spiekman; Joris A van Dongen; Joep C Willemsen; Delia L Hoppe; Berend van der Lei; Martin C Harmsen Journal: J Tissue Eng Regen Med Date: 2017-02-03 Impact factor: 3.963