Journal
STEM CELLS TRANSLATIONAL MEDICINE
Volume 5, Issue 10, Pages 1425-1439Publisher
OXFORD UNIV PRESS
DOI: 10.5966/sctm.2015-0367
Keywords
Myofibroblast; Transforming growth factor-beta; Exosome; Mesenchymal stem cells; MicroRNA
Categories
Funding
- National Natural Science Foundation of China [31471390, 31201110, 81272119, 81301644]
- Foundation of Science and Technology Commission of Shanghai Municipality [13JC1407101, 13ZR1334800]
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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.
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