期刊
NATURE MATERIALS
卷 16, 期 3, 页码 379-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT4780
关键词
-
类别
资金
- Canadian Institutes of Health Research CIHR [210820, 286920, 286720]
- Collaborative Health Research Programme (CIHR/NSERC grants) [1004005, 413783]
- Canada Foundation for Innovation and Ontario Research Fund (CH/ORF) [26653]
- CIHR [MOP-106625, 130463]
- Canadian Foundation of Innovation
- Kidney Foundation of Canada
- European Union [237946]
Expansion on stiff culture substrates activates pro-fibrotic cell programs that are retained by mechanical memory. Here, we show that priming on physiologically soft silicone substrates suppresses fibrogenesis and desensitizes mesenchymal stem cells ( MSCs) against subsequent mechanical activation in vitro and in vivo, and identify the microRNA miR-21 as a long-term memory keeper of the fibrogenic program in MSCs. During stiff priming, miR-21 levels were gradually increased by continued regulation through the acutely mechanosensitive myocardin-related transcription factor-A ( MRTF-A/MLK-1) and remained high over 2 weeks after removal of the mechanical stimulus. Knocking down miR-21 once by the end of the stiff-priming period was sufficient to erase the mechanical memory and sensitize MSCs to subsequent exposure to soft substrates. Soft priming and erasing mechanical memory following cell culture expansion protects MSCs from fibrogenesis in the host wound environment and increases the chances for success of MSC therapy in tissue- repair applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据