Cardio-renal Exosomes in Myocardial Infarction Serum Regulate Proangiogenic Paracrine Signaling in Adipose Mesenchymal Stem Cells

作者：Lei Gao, Shuya Mei, Shuning Zhang, Qing Qin, Hao Ran Li, Yiteng Liao, Huimin Fan, Zhongmin Liu, Hongming Zhu · 发表于：Theranostics · 年份：2019 · DOI：10.7150/thno.37678 · 被引用次数：81 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

Rationale: Mesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration.However, the molecular mechanisms underlying MSCs activation remain largely unknown, thus hindering their clinical translation.Exosomes are small vesicles that act as intercellular messengers, and their potential for stem cell activation in pathological conditions has not been fully characterized yet.Here, we aim to investigate whether serum exosomes are involved in the remote activation of MSCs after myocardial infarction (MI).Methods: We established MI mouse model by ligating the left anterior descending branch of the coronary artery.Afterwards, serum exosomes were isolated from control (Con Exo) and MI mice (MI Exo) by differential centrifugation.Exosomes were characterized through transmission electron microscopy and nanoparticle tracking analysis.The cell proliferation rate was evaluated by CCK-8 and EdU incorporation assays.Exosomal miRNA and protein levels were assessed using qRT-PCR and western blotting, respectively.VEGF levels in the supernatant and serum were quantified by ELISA.Matrigel plug and tube formation assays were used to evaluate angiogenesis.To explore miR-1956 roles, overexpression and knock-down experiments were performed using mimic and inhibitor, respectively.Finally, miR-1956 target genes were confirmed using the luciferase reporter assay.Results: Both types of exosomes exhibited typical characteristics and could be internalized by adipose-derived MSCs (A...