Exosomes derived from pro-inflammatory bone marrow-derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization

被引:286
作者
Xu, Ruqin [1 ]
Zhang, Fangcheng [1 ]
Chai, Renjie [1 ]
Zhou, Wenyi [1 ]
Hu, Ming [1 ]
Liu, Bin [1 ]
Chen, Xuke [1 ]
Liu, Mingke [1 ]
Xu, Qiong [1 ]
Liu, Ningning [1 ]
Liu, Shiming [1 ]
机构
[1] Guangzhou Med Univ, Affiliated Hosp 2, State Key Lab Resp Dis, Guangzhou Inst Cardiovasc Dis,Guangdong Key Lab V, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
exosomes; inflammation; macrophage polarization; mesenchymal stem cells; myocardial infarction; PARTICLE-SIZE; KAPPA-B; ACTIVATION; INFARCTION; EFFICACY; THERAPY; REPAIR; TRANSPLANTATION; ROLES; M1;
D O I
10.1111/jcmm.14635
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Exosomes are served as substitutes for stem cell therapy, playing important roles in mediating heart repair during myocardial infarction injury. Evidence have indicated that lipopolysaccharide (LPS) pre-conditioning bone marrow-derived mesenchymal stem cells (BMSCs) and their secreted exosomes promote macrophage polarization and tissue repair in several inflammation diseases; however, it has not been fully elucidated in myocardial infarction (MI). This study aimed to investigate whether LPS-primed BMSC-derived exosomes could mediate inflammation and myocardial injury via macrophage polarization after MI. Here, we found that exosomes derived from BMSCs, in both Exo and L-Exo groups, increased M2 macrophage polarization and decreased M1 macrophage polarization under LPS stimulation, which strongly depressed LPS-dependent NF-kappa B signalling pathway and partly activated the AKT1/AKT2 signalling pathway. Compared with Exo, L-Exo had superior therapeutic effects on polarizing M2 macrophage in vitro and attenuated the post-infarction inflammation and cardiomyocyte apoptosis by mediating macrophage polarization in mice MI model. Consequently, we have confidence in the perspective that low concentration of LPS pre-conditioning BMSC-derived exosomes may develop into a promising cell-free treatment strategy for clinical treatment of MI.
引用
收藏
页码:7617 / 7631
页数:15
相关论文
共 60 条
[1]
Human Placental Mesenchymal Stem Cells (pMSCs) Play a Role as Immune Suppressive Cells by Shifting Macrophage Differentiation from Inflammatory M1 to Anti-inflammatory M2 Macrophages [J].
Abumaree, M. H. ;
Al Jumah, M. A. ;
Kalionis, B. ;
Jawdat, D. ;
Al Khaldi, A. ;
Abomaray, F. M. ;
Fatani, A. S. ;
Chamley, L. W. ;
Knawy, B. A. .
STEM CELL REVIEWS AND REPORTS, 2013, 9 (05) :620-641
[2]
Regulatory Role of Dendritic Cells in Postinfarction Healing and Left Ventricular Remodeling [J].
Anzai, Atsushi ;
Anzai, Toshihisa ;
Nagai, Shigenori ;
Maekawa, Yuichiro ;
Naito, Kotaro ;
Kaneko, Hidehiro ;
Sugano, Yasuo ;
Takahashi, Toshiyuki ;
Abe, Hitoshi ;
Mochizuki, Satsuki ;
Sano, Motoaki ;
Yoshikawa, Tsutomu ;
Okada, Yasunori ;
Koyasu, Shigeo ;
Ogawa, Satoshi ;
Fukuda, Keiichi .
CIRCULATION, 2012, 125 (10) :1234-1245
[3]
Post-Infarction Inflammation and Left Ventricular emodeling - A Double-Edged Sword [J].
Anzai, Toshihisa .
CIRCULATION JOURNAL, 2013, 77 (03) :580-587
[4]
Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization [J].
Arranz, Alicia ;
Doxaki, Christina ;
Vergadi, Eleni ;
de la Torre, Yeny Martinez ;
Vaporidi, Katerina ;
Lagoudaki, Eleni D. ;
Ieronymaki, Eleftheria ;
Androulidaki, Ariadne ;
Venihaki, Maria ;
Margioris, Andrew N. ;
Stathopoulos, Efstathios N. ;
Tsichlis, Philip N. ;
Tsatsanis, Christos .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (24) :9517-9522
[5]
Barile Lucio, 2017, Stem Cell Investig, V4, P93, DOI 10.21037/sci.2017.11.06
[6]
Assessment of safety and efficacy of mesenchymal stromal cell therapy in preclinical models of acute myocardial infarction: a systematic review protocol [J].
Barron, Carly C. ;
Lalu, Manoj M. ;
Stewart, Duncan J. ;
Fergusson, Dean ;
Yang, Homer ;
Moher, David ;
Liu, Peter ;
Mazer, David ;
Devereaux, P. J. ;
McIntyre, Lauralyn .
SYSTEMATIC REVIEWS, 2017, 6
[7]
Targeting Macrophage Subsets for Infarct Repair [J].
Ben-Mordechai, Tamar ;
Palevski, Dahlia ;
Glucksam-Galnoy, Yifat ;
Elron-Gross, Inbar ;
Margalit, Rimona ;
Leor, Jonathan .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2015, 20 (01) :36-51
[8]
Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment [J].
Cassano, Jennifer M. ;
Schnabel, Lauren, V ;
Goodale, Margaret B. ;
Fortier, Lisa A. .
STEM CELL RESEARCH & THERAPY, 2018, 9
[9]
Bone Marrow-Derived Mesenchymal Stem Cells Exert Diverse Effects on Different Macrophage Subsets [J].
Chen, Bin ;
Ni, Yanhong ;
Liu, Baying ;
Zhang, Yangheng ;
Yan, Fuhua .
STEM CELLS INTERNATIONAL, 2018, 2018
[10]
Focus on Mesenchymal Stem Cell-Derived Exosomes: Opportunities and Challenges in Cell-Free Therapy [J].
Cheng, Lin ;
Zhang, Kun ;
Wu, Shuying ;
Cui, Manhua ;
Xu, Tianmin .
STEM CELLS INTERNATIONAL, 2017, 2017