随着高通量蛋白质组学和基因组学和对旁分泌机制理解的发展,尤其是在癌症和发育,外泌体生物学领域经历了一个范式转变(paradigm shift);细胞分泌的颗粒曾一度被认为是参与废物排泄,而现在被广泛认为是生物体内短距离和长距离细胞间交流的高度保守的途径。所有真核细胞类型包括造血细胞、上皮细胞、神经细胞、干细胞、脂肪细胞和癌症细胞均可在培养条件下分泌外泌体。目前已证明在所有真核生物类群,从单细胞真菌变形原生生物,植物,动物都可产生外泌体。在体内,可以从所有体液,包括血液、腹水、脑脊液、唾液、牛奶、甚至尿液中分离得到外泌体。这些囊泡传输多种信号分子,尤其是蛋白质,mRNA,非编码RNA,尤其是microRNAs。此外,在各种健康与疾病模型中都发现了这些细胞外膜泡通过传递其分子而扮演着重要的角色。现在有大量的证据表明,外泌体能介导自分泌、旁分泌和内分泌功能。外泌体的第一个临床转化在诊断领域:从血液或尿液分离的外泌体可以用作为疾病、癌症和中枢神经系统疾病、心脏病的诊断和预后的指标。细胞治疗的目标就是组织的再生,近期的一些外泌体在心血管疾病中的作用的研究激发了人们对细胞治疗认识的新视角:外泌体可能在细胞治疗中起着部分甚至全部治疗效果。
外泌体在组织损伤中的作用
原文来源:Ibrahim, A. and E. Marban (2015). "Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology." Annu Rev Physiol.
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作者简介
Eduardo Marban,西奈山医学院心脏研究所(Cedars-Sinai Heart Institute)首任所长、前任Circulation Research杂志主编Eduardo Marban在近期的Annu Rev Physiol杂志(IF=18.51)上对外泌体的基础生物学及其在心血管生理中的作用做了总结,其中包括外泌体的定义、形成、成分等基础方面,外泌体在心肌肥大、心室重构、心律不齐和心肌病等心血管病理生理方面,和间充质干细胞、造血干细胞、心脏前体细胞和Cardiosphere来源的细胞的外泌体在作为下一代治疗试剂方面的研究进展。
Eduardo Marban已发表的外泌体相关论文:
- Aminzadeh, M. A., et al. (2015). "Exosome-mediated Reversal of Duchenne Cardiomyopathy." Circulation-Abstract.
- de Couto, G., et al. (2015). "Cardiosphere-derived Cell Exosomes Confer Acute Cardioprotection Following Ischemia-reperfusion Injury Through Macrophage Polarization (Best of Basic Science Abstract)."Circulation 132(Suppl 3): A16991-A16991.
- Gallet, R., et al. (2015). "Open-Chest Intramyocardial Delivery of Exosomes From Cardiosphere-Derived Cells (CDCs) Mimics Cellular Postconditioning: Decreased Infarct Size and Improved Perfusion in a Pig Model of Acute Myocardial Infarction." Circulation 132(Suppl 3): A15649-A15649.
- Gallet, R., et al. (2015). "Percutaneous Intra-myocardial Injection of Exosomes From Cardiosphere-derived Cells (CDCs) Halts Adverse Remodeling and Decreases Scar Size in Porcine Ischemic Cardiomyopathy." Circulation 132(Suppl 3): A16214-A16214.
- Ibrahim, A. and E. Marban (2015). "Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology." Annu Rev Physiol.
- Ibrahim, A. G.-E., et al. (2014). "Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy." Stem Cell Reports 2(5): 606-619.
- Makkar, R. R., et al. (2012). "Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial." The Lancet 379(9819): 895-904.
- Tseliou, E., et al. (2014). "Regenerative Effects of Exosomes Secreted by Cardiospheres in a Rat Model of Chronic Myocardial Infarction Are Mimicked by Exosome-primed Fibroblasts." Circulation130(Suppl 2): A15483-A15483.
- Tseliou, E., et al. (2015). "Fibroblasts Rendered Antifibrotic, Antiapoptotic, and Angiogenic by Priming With Cardiosphere-Derived Extracellular Membrane Vesicles." J Am Coll Cardiol 66(6): 599-611.
- Xie, Y., et al. (2014). "Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells." Stem Cells 32(9): 2397-2406.