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

• Published in: International journal of molecular sciences Vol. 15; no. 1; p. 605
• Main Authors: Jun, Eun Kyoung, Zhang, Qiankun, Yoon, Byung Sun, Moon, Jai-Hee, Lee, Gilju, Park, Gyuman, Kang, Phil Jun, Lee, Jung Han, Kim, Areee, You, Seungkwon
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.01.2014
• Subjects: Hypoxia; Molecular biology; Stem cells; Wound healing
• ISSN: 1661-6596; 1422-0067
• DOI: 10.3390/ijms15010605

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.