Bin Zhao1, Jia-Qi Liu1, Chen Yang1, Zhao Zheng1, Qin Zhou1, Hao Guan1, Lin-Lin Su2, Da-Hai Hu3. 1. Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. 2. Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: linlinsu@fmmu.edu.cn. 3. Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: hudhai@fmmu.edu.cn.
Abstract
BACKGROUND AIMS: Keloids are raised dermal scars that extend beyond the boundaries of the initial injury. To date, there is no treatment to erase scars completely in humans. Growing evidence has shown that the human amniotic epithelial cells have anti-fibrotic properties and can reduce the fibrosis of lung and liver. However, it is unknown whether and how they can influence human keloids. The aim of this study was to investigate whether factors secreted by human amniotic epithelial cells have anti-fibrotic effects on human keloids and to clarify the potential transduction mechanism. METHODS: Human amniotic epithelial cells were isolated and identified both with flow cytometry and immunofluorescent. The α-smooth muscle actin, collagen-I and III gene and protein expression of transforming growth factor (TGF)-β1-treated human adult dermal fibroblasts were partly abolished by human amniotic epithelial cells conditioned medium through stimulating the expression of matrix metalloproteinase (MMP). Furthermore, human amniotic epithelial cells conditioned medium effectively attenuated nuclear import of the Smad2/3 complex. RESULTS: Soluble human leukocyte antigen G, a human amniotic epithelial cell-derived factor, significantly decreased collagen production in TGF-β1-induced human dermal fibroblasts, although the effect on collagen production was less than that of human amniotic epithelial cell-conditioned medium. CONCLUSIONS: This study demonstrates that human amniotic epithelial cells conditioned medium could down-regulate the expression of fibrosis-related molecules by regulating MMP and tissue inhibitor of metalloproteinase levels, and suppress TGF-β1-induced fibroblast transition, in which the TGF-β1/Smad3 pathway is likely involved. These findings suggest that human amniotic epithelial cells are a potential therapeutic compound for the treatment of keloids.
BACKGROUND AIMS: Keloids are raised dermal scars that extend beyond the boundaries of the initial injury. To date, there is no treatment to erase scars completely in humans. Growing evidence has shown that the human amniotic epithelial cells have anti-fibrotic properties and can reduce the fibrosis of lung and liver. However, it is unknown whether and how they can influence human keloids. The aim of this study was to investigate whether factors secreted by human amniotic epithelial cells have anti-fibrotic effects on human keloids and to clarify the potential transduction mechanism. METHODS:Human amniotic epithelial cells were isolated and identified both with flow cytometry and immunofluorescent. The α-smooth muscle actin, collagen-I and III gene and protein expression of transforming growth factor (TGF)-β1-treated human adult dermal fibroblasts were partly abolished by human amniotic epithelial cells conditioned medium through stimulating the expression of matrix metalloproteinase (MMP). Furthermore, human amniotic epithelial cells conditioned medium effectively attenuated nuclear import of the Smad2/3 complex. RESULTS: Soluble human leukocyte antigen G, a human amniotic epithelial cell-derived factor, significantly decreased collagen production in TGF-β1-induced human dermal fibroblasts, although the effect on collagen production was less than that of human amniotic epithelial cell-conditioned medium. CONCLUSIONS: This study demonstrates that human amniotic epithelial cells conditioned medium could down-regulate the expression of fibrosis-related molecules by regulating MMP and tissue inhibitor of metalloproteinase levels, and suppress TGF-β1-induced fibroblast transition, in which the TGF-β1/Smad3 pathway is likely involved. These findings suggest that human amniotic epithelial cells are a potential therapeutic compound for the treatment of keloids.
Authors: William Sievert; Rebecca Lim; Mihiri Goonetilleke; Nathan Kuk; Jeanne Correia; Alex Hodge; Gregory Moore; Michael P Gantier; George Yeoh Journal: Stem Cell Res Ther Date: 2021-07-28 Impact factor: 6.832