title: Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a.
abstract: 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.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China hanqinhanqin@126.com zhaochunhua@vip.163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China Peking Union Medical College Hospital, 1# Shuaifuyuan, Beijing 100032, People's Republic of China hanqinhanqin@126.com zhaochunhua@vip.163.com.
authors.forename: Robert Chunhua
authors.identifier: 0000-0001-5740-4506
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002469:Cell Separation; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: Angiogenesis; DLL4; Exosome; miR-125a