• Jianlan Liu, Jie Ren, Lina Su, Shimeng Cheng, Jing Zhou, Xiaolu Ye, Yabin Dong, Silei Sun, Fazhi Qi, Zhifei Liu, Jonathon Pleat, Hongjun Zhai, and Ningwen Zhu.
• Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Plastic, Reconstructive and Burns Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
• Burns. 2018 Mar 1; 44 (2): 370-385.

BackgroundHuman adipose tissue-derived mesenchymal stem cells (ASCs) have potential utility as modulators of the regeneration of tissue that is inflamed or scarred secondary to injuries such as burns or trauma. However, the effect of ASCs on one particular type of scarring, keloidal disease, remains unknown. The absence of an optimal model for investigation has hindered the development of an effective therapy using ASCs for keloids.ObjectiveTo investigate the influence of ASCs on angiogenesis, extracellular matrix deposition, and inflammatory cell influx in keloids.MethodsWe analyzed the proliferation, migration, and apoptosis of human keloid-derived fibroblasts treated with a starvation-induced, conditioned medium from ASCs (ASCs-CM). This was achieved by Brdu proliferation assay, a validated co-culture migration assay, and flow cytometry, respectively. To assess the change in phenotype to a pro-fibrotic state, fibroblasts were analyzed by real-time PCR and contraction assay. A keloid implantation animal model was used to assess the paracrine effect of ASCs histochemically and immunohistochemically on scar morphology, collagen deposition, inflammatory cell composition, and blood vessel density. In tandem, an antibody-based array was used to identify protein concentration in the presence of ASCs-CM at time point 0, 24, and 48h.ResultsASCs-CM inhibited the proliferation and collagen synthesis of human keloid-derived fibroblasts. ASCs-CM was associated with reduced inflammation and fibrosis in the keloid implantation model. Thirty-four cytokines were differentially regulated by ASCs-CM at 24h. These included molecules associated with apoptosis, matrix metalloproteases, and their inhibitors. The same molecules were present at relatively higher concentrations at the 48h timepoint.ConclusionThese results suggest that ASCs are associated with the inhibition of fibrosis in keloids by a paracrine effect. This phenomenon may have utility as a therapeutic approach in the clinical environment.Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

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