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

被引：147

作者：

Jun, Eun Kyoung ^{[1
]}

Zhang, Qiankun ^{[1
]}

Yoon, Byung Sun ^{[1
]}

Moon, Jai-Hee ^{[1
]}

Lee, Gilju ^{[1
]}

Park, Gyuman ^{[1
]}

Kang, Phil Jun ^{[1
]}

Lee, Jung Han ^{[1
]}

Kim, Areee ^{[2
]}

You, Seungkwon ^{[1
]}

机构：

[1] Korea Univ, Coll Life Sci & Biotechnol, Lab Cell Funct Regulat, Seoul 136717, South Korea

[2] Korea Univ, Dept Pathol, Coll Med, Guro Hosp, Seoul 152703, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2014年 / 15卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

PI3K/AKT; hypoxia; TGF-beta/SMAD2; wound healing; amniotic fluid-derived mesenchymal stem cells (AF-MSCs); UMBILICAL-CORD BLOOD; BONE-MARROW; IN-VITRO; STROMAL CELLS; TUMOR ANGIOGENESIS; EPITHELIAL-CELLS; OXYGEN-TENSION; UP-REGULATION; GROWTH; EXPRESSION;

D O I：

10.3390/ijms15010605

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta 1, 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-beta/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-beta/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-beta/SMAD2 and PI3K/AKT pathways.

引用

页码：605 / 628

页数：24

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