Int. J. Mol. Sci. 2014, 15(1), 605-628; doi:10.3390/ijms15010605
Article

Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways

Received: 12 November 2013; in revised form: 21 December 2013 / Accepted: 2 January 2014 / Published: 6 January 2014
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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 cell-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 AF-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, AF-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 TGF-β/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-β/SMAD2 and PI3K/AKT pathways.
Keywords: hypoxia; amniotic fluid-derived mesenchymal stem cells (AF-MSCs); wound healing; PI3K/AKT; TGF-β/SMAD2
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MDPI and ACS Style

Jun, E.K.; Zhang, Q.; Yoon, B.S.; Moon, J.-H.; Lee, G.; Park, G.; Kang, P.J.; Lee, J.H.; Kim, A.; You, S. Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways. Int. J. Mol. Sci. 2014, 15, 605-628.

AMA Style

Jun EK, Zhang Q, Yoon BS, Moon J-H, Lee G, Park G, Kang PJ, Lee JH, Kim A, You S. Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways. International Journal of Molecular Sciences. 2014; 15(1):605-628.

Chicago/Turabian Style

Jun, Eun K.; Zhang, Qiankun; Yoon, Byung S.; Moon, Jai-Hee; Lee, Gilju; Park, Gyuman; Kang, Phil J.; Lee, Jung H.; Kim, Areee; You, Seungkwon. 2014. "Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways." Int. J. Mol. Sci. 15, no. 1: 605-628.

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