Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-β/SMAD2 and PI3K/AKT pathways

Eun Kyoung Jun, Qiankun Zhang, Byung Sun Yoon, Jai Hee Moon, Gilju Lee, Gyuman Park, Phil Jun Kang, Jung Han Lee, Aeree Kim, Seungkwon You

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68 Citations (Scopus)


In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem ce-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of A-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-β1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, A-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and LY294002, inhibitors of TGF-β/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of T-β/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of h-duced paracrine factors via activation of TGF-β/SMAD2 and PI3K/AKT pathways.

Original languageEnglish
Pages (from-to)605-628
Number of pages24
JournalInternational Journal of Molecular Sciences
Issue number1
Publication statusPublished - 2014 Jan 6



  • Amniotic fluid-derived mesenchymal stem cells(AF-MASs)
  • Hypoxia
  • PI3K/AKT
  • TGF-β/SMAD2
  • Wound healing

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry

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