Exosomes secreted by hypoxic cardiosphere-derived cells enhance tube formation and increase pro-angiogenic miRNA

被引:108
作者
Namazi, Helia [1 ,2 ]
Mohit, Elham [1 ,3 ]
Namazi, Iman [4 ]
Rajabi, Sarah [5 ]
Samadian, Azam [5 ]
Hajizadeh-Saffar, Ensiyeh [5 ]
Aghdami, Nasser [5 ]
Baharvand, Hossein [5 ]
机构
[1] Shahid Beheshti Univ Med Sci, Dept Pharmaceut Biotechnol, Sch Pharm, Tehran, Iran
[2] Shahid Beheshti Univ Med Sci, Students Res Comm, Tehran, Iran
[3] Shahid Beheshti Univ Med Sci, Prot Technol Res Ctr, Tehran, Iran
[4] Mashhad Univ Med Sci, Sch Med, Mashhad, Iran
[5] ACECR, Dept Stem Cells & Dev Biol, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran, Iran
基金
美国国家科学基金会;
关键词
angiogenesis; cardiosphere-derived cells; exosomes; microRNA; CARDIAC STEM-CELLS; ENDOTHELIAL-CELLS; GENE-EXPRESSION; TYROSINE KINASE; MICRORNAS; IDENTIFICATION; THERAPY; REPAIR; AGENTS;
D O I
10.1002/jcb.26621
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Exosomes are required for the regenerative effects of human cardiosphere-derived cells (CDCs). Studies show that they mimic the cardioprotective benefits of CDCs in rodents and porcine myocardial infarction (MI) models. Hypoxic preconditioning of stem cells increases the cardioprotective effects of exosomes in MI models by enhancing angiogenesis. Several exosomal microRNAs (miRNAs) up-regulate in response to hypoxia and play a role in cardioprotective and pro-angiogenic effects. In this study, we have demonstrated that human CDCs secreted exosomes under hypoxic conditions (1% O-2 for 2 days) enhanced tube formation by human umbilical vein endothelial cells (HUVECs) at a concentration of 25 mu g/mL. Pro-angiogenic exosomal miRNAs including miR-126, miR-130a, and miR-210 showed a substantial increase (>2-, >2-, and >4-fold, respectively) in the hypoxic exosomes compared to normoxic CDC-derived exosomes. Our study suggested a significant benefit of hypoxic CDC exosomes for the treatment of cardiac diseases by induction of angiogenesis via enrichment of pro-angiogenic exosomal miRNAs.
引用
收藏
页码:4150 / 4160
页数:11
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