title: Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-β/SMAD2 and PI3K/Akt pathways.
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.
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. ek-young@hanmail.net.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Jun
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. qkzhang0915@gmail.com.
authors.forename: Qiankun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. biosun302@korea.ac.kr.
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Yoon
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. moonjaihi@hanmail.net.
authors.forename: Jai-Hee
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. ggang1979@hanmail.net.
authors.forename: Gilju
authors.initials: G
authors.lastname: Lee
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. legnaym@korea.ac.kr.
authors.forename: Gyuman
authors.initials: G
authors.lastname: Park
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. rebeast@korea.ac.kr.
authors.forename: Phil Jun
authors.initials: PJ
authors.lastname: Kang
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. ano112@nate.com.
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. ark@korea.ac.kr.
authors.forename: Areee
authors.initials: A
authors.lastname: Kim
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-717, Korea. bioseung@korea.ac.kr.
authors.forename: Seungkwon
authors.initials: S
authors.lastname: You
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C519132:2-(5-benzo(1,3)dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride; D052117:Benzodioxoles; D002867:Chromones; D017077:Culture Media, Conditioned; D007093:Imidazoles; D009025:Morpholines; D011725:Pyridines; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one