Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 11, Pages 2182-2189Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.170373
Keywords
Exosome; miR-125a; DLL4; Angiogenesis
Categories
Funding
- National Key Scientific Program of China [2011CB964901]
- National Collaborative Innovation Program
- National Science and Technology Major Project for Drug Research and Development [2014ZX0910104]
- National Science and Technology Major Project of the Ministry of Science and Technology of the People's Republic of China [2014ZX09101042]
- Key Program for Beijing Municipal Natural Science Foundation [7141006]
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Angiogenesis plays crucial roles in various physiological processes including wound healing and tissue repair. It requires a tight interaction between endothelial cells and their surrounding environment. Mesenchymal stem cells (MSCs), one of the non-endothelial cell types present in the perivascular environment, have been shown to secret exosomes to modulate intercellular communications between MSCs and their target cells. In this study, we initially isolated exosomes secreted by human adipose-derived MSCs (adMSC-Exo) and examined their roles in angiogenesis. We found that adMSC-Exo could be taken up by endothelial cells and significantly promote angiogenesis in vitro and in vivo. Further study showed that miR-125a was enriched in adMSC-Exo, and repressed the expression of the angiogenic inhibitor delta-like 4 (DLL4) by targeting its 3' untranslated region. Additionally, adMSC-Exo and its exosomal transferred miR-125a could repress DLL4 expression and modulate endothelial cell angiogenesis through promoting formation of endothelial tip cells. In conclusion, our study indicates that adMSC-Exo can transfer miR-125a to endothelial cells and promote angiogenesis by repressing DLL4. adMSC-Exo, as a pro-angiogenic factor, might be a promising candidate for therapeutical tissue repair.
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