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Exosomes derived from adipose tissue stem cells regenerate ischemic myocardium following intravenous administration
Author(s) -
Wang Min,
Xu Jie,
Liu Min,
Wang YiGang,
Ashraf Muhammad,
Xu Meifeng
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.716.3
Subject(s) - mesenchymal stem cell , adipose tissue , ligation , myocardial infarction , cardiac function curve , microvesicles , bone marrow , medicine , exosome , infarction , stem cell , artery , chemistry , cardiology , pathology , heart failure , microbiology and biotechnology , biology , microrna , biochemistry , gene
Objective Exosomes (EXO) are nanosized bi‐lipid‐layered vesicles that contain proteins, mRNAs, and miRs. Increased evidence indicates that EXO play an important role in intercellular communication and cardiac repair. They have long circulating half‐life and cellular effects. EXO can be administered intravenously (iv) without risk of microvasculature entrapment. Our previous studies indicated that mesenchymal stem cells (MSCs) isolated from adipose tissue (AD‐MSCs) proliferated faster and secreted more EXO compared to those derived from bone marrow (BM‐MSCs). In this study, we investigated if intravenous administration of AD‐EXO can improve cardiac function and regenerate ischemic myocardium via native cardiomyocytes (CMs) protection. Methods and Results MSCs were harvested from adipose tissue of 6–8 weeks old C57BL/6 mice. EXO were collected from MSC conditional medium by ultracentrifugation, and were characterized by morphology and surface markers. Mouse myocardial infarction (MI) was created by ligation of left anterior descending (LAD) coronary artery. EXO (50 μg) were injected through tail vein every two days for a total of 2 or 4 times, respectively. Primary CMs were obtained from ventricles of 2‐day‐old rats. Ischemic injury was mimicked by exposing CMs to hypoxic culture (1% O 2 , 5%CO 2 , and 94% N 2 ). We found that 1) Left ventricular function following LAD ligation was significantly improved and infarction size was significantly reduced in mice injected with AD‐EXO (50 μg) for a total of 4 times. 2) Distribution of AD‐EXO in heart was clearly observed following injection of pre‐labeled EXO with PKH26. 3) AD‐EXO significantly protected CMs against hypoxia induced injury. Conclusions EXO derived from AD‐MSCs can be successfully delivered to myocardium following intravenous administration, which results in improved cardiac function and reduced infarction size in mouse MI model. Support or Funding Information This work was supported by NIH Grants HL114654, and HL140962 (M. Xu). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .