Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing

被引：561

作者：

Fang, Shuo ^{[1
]}

Xu, Chen ^{[3
]}

Zhang, Yuntong ^{[2
]}

Xue, Chunyu ^{[1
]}

Yang, Chao ^{[1
]}

Bi, Hongda ^{[1
]}

Qian, Xijing ^{[4
]}

Wu, Minjuan ^{[5
]}

Ji, Kaihong ^{[5
,6
]}

Zhao, Yunpeng ^{[5
,6
]}

Wang, Yue ^{[5
,6
]}

Liu, Houqi ^{[5
,6
]}

Xing, Xin ^{[1
]}

机构：

[1] Second Mil Med Univ, Shanghai Changhai Hosp, Dept Plast & Reconstruct, 168th Chang Hai Rd, Shanghai 200433, Peoples R China

[2] Second Mil Med Univ, Shanghai Changhai Hosp, Dept Emergency & Trauma, Shanghai, Peoples R China

[3] Second Mil Med Univ, Changzheng Hosp, Dept Spinal Surg, Shanghai, Peoples R China

[4] Second Mil Med Univ, Dept Microbiol, Shanghai Key Lab Med Biodef, Shanghai, Peoples R China

[5] Second Mil Med Univ, Res Ctr Dev Biol, 800th Xiangyin Rd, Shanghai 200433, Peoples R China

[6] Second Mil Med Univ, Translat Med Ctr, 800th Xiangyin Rd, Shanghai 200433, Peoples R China

来源：

STEM CELLS TRANSLATIONAL MEDICINE | 2016年 / 5卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Myofibroblast; Transforming growth factor-beta; Exosome; Mesenchymal stem cells; MicroRNA; TGF-BETA; FIBROSIS; PROLIFERATION; TRANSMISSION; FIBROBLASTS; CONTRACTION; MIGRATION; RESPONSES;

D O I：

10.5966/sctm.2015-0367

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Excessive scar formation caused by myofibroblast aggregations is of great clinical importance during skin wound healing. Studies have shown that mesenchymal stem cells (MSCs) can promote skin regeneration, but whether MSCs contribute to scar formation remains undefined. We found that umbilical cord-derived MSCs (uMSCs) reduced scar formation and myofibroblast accumulation in a skin-defect mouse model. We found that these functions were mainly dependent on uMSC-derived exosomes (uMSC-Exos) and especially exosomal microRNAs. Through high-throughput RNA sequencing and functional analysis, we demonstrated that a group of uMSC-Exos enriched in specific microRNAs (miR-21, -23a, -125b, and -145) played key roles in suppressing myofibroblast formation by inhibiting the transforming growth factor-beta 2/SMAD2 pathway. Finally, using the strategy we established to block miRNAs inside the exosomes, we showed that these specific exosomal miRNAs were essential for the myofibroblast-suppressing and anti-scarring functions of uMSCs both in vitro and in vivo. Our study revealed a novel role of exosomal miRNAs in uMSC-mediated therapy, suggesting that the clinical application of uMSC-derived exosomes might represent a strategy to prevent scar formation during wound healing.

引用

页码：1425 / 1439

页数：15

共 41 条

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