The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation Therapeutics

Overview

Journal J Am Coll Cardiol

Specialty Cardiology & Vascular Diseases

Date 2018 Jan 13

PMID 29325643

Citations 79

Authors

Eduardo Marban

Affiliations

Soon will be listed here.

Abstract

Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to recapitulate the benefits of cells and more. As durable azoic entities, exosomes have numerous practical and conceptual advantages over cells. Will cells end up just being used to manufacture exosomes, or will they find lasting value as primary therapeutic agents? Here, a venerable natural process-the generation of honey-serves as an instructive parable. Flowers make nectar, which bees collect and process into honey. Cells make conditioned medium, which laboratory workers collect and process into exosomes. Unlike flowers, honey is durable, compact, and nutritious, but these facts do not negate the value of flowers themselves. The parallels suggest new ways of thinking about next-generation therapeutics.

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References

Roth G, Johnson C, Abajobir A, Abd-Allah F, Abera S, Abyu G . Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017; 70(1):1-25. PMC: 5491406. DOI: 10.1016/j.jacc.2017.04.052. View

Marinescu K, Uriel N, Mann D, Burkhoff D . Left ventricular assist device-induced reverse remodeling: it's not just about myocardial recovery. Expert Rev Med Devices. 2016; 14(1):15-26. PMC: 5541390. DOI: 10.1080/17434440.2017.1262762. View

Lee C, Mitsialis S, Aslam M, Vitali S, Vergadi E, Konstantinou G . Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012; 126(22):2601-11. PMC: 3979353. DOI: 10.1161/CIRCULATIONAHA.112.114173. View

Kordelas L, Rebmann V, Ludwig A, Radtke S, Ruesing J, Doeppner T . MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia. 2014; 28(4):970-3. DOI: 10.1038/leu.2014.41. View

de Couto G, Gallet R, Cambier L, Jaghatspanyan E, Makkar N, Dawkins J . Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning. Circulation. 2017; 136(2):200-214. PMC: 5505791. DOI: 10.1161/CIRCULATIONAHA.116.024590. View

van der Pol E, Boing A, Harrison P, Sturk A, Nieuwland R . Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 2012; 64(3):676-705. DOI: 10.1124/pr.112.005983. View

Nigro P, Bassetti B, Cavallotti L, Catto V, Carbucicchio C, Pompilio G . Cell therapy for heart disease after 15 years: Unmet expectations. Pharmacol Res. 2017; 127:77-91. DOI: 10.1016/j.phrs.2017.02.015. View

Gallet R, de Couto G, Simsolo E, Valle J, Sun B, Liu W . Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation. JACC Basic Transl Sci. 2016; 1(1-2):14-28. PMC: 4834906. DOI: 10.1016/j.jacbts.2016.01.003. View

Hirshman B, Kras R, Akers J, Carter B, Chen C . Extracellular Vesicles in Molecular Diagnostics: An Overview with a Focus on CNS Diseases. Adv Clin Chem. 2016; 76:37-53. DOI: 10.1016/bs.acc.2016.05.005. View

10.

Ni H, Xu J . Recent Trends in Heart Failure-related Mortality: United States, 2000-2014. NCHS Data Brief. 2016; (231):1-8. View

11.

Chimenti I, Ruckdeschel Smith R, Li T, Gerstenblith G, Messina E, Giacomello A . Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010; 106(5):971-80. PMC: 4317351. DOI: 10.1161/CIRCRESAHA.109.210682. View

12.

Lai R, Arslan F, Lee M, Sze N, Choo A, Chen T . Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010; 4(3):214-22. DOI: 10.1016/j.scr.2009.12.003. View

13.

Gray W, French K, Ghosh-Choudhary S, Maxwell J, Brown M, Platt M . Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ Res. 2014; 116(2):255-63. PMC: 4338016. DOI: 10.1161/CIRCRESAHA.116.304360. View

14.

Peche H, Heslan M, Usal C, Amigorena S, Cuturi M . Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection. Transplantation. 2003; 76(10):1503-10. DOI: 10.1097/01.TP.0000092494.75313.38. View

15.

Bang C, Batkai S, Dangwal S, Gupta S, Foinquinos A, Holzmann A . Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014; 124(5):2136-46. PMC: 4001534. DOI: 10.1172/JCI70577. View

16.

Lotvall J, Hill A, Hochberg F, Buzas E, Di Vizio D, Gardiner C . Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014; 3:26913. PMC: 4275645. DOI: 10.3402/jev.v3.26913. View

17.

Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, Batte K . Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood. 2012; 121(6):984-95. PMC: 3567345. DOI: 10.1182/blood-2011-08-374793. View

18.

Sahoo S, Klychko E, Thorne T, Misener S, Schultz K, Millay M . Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res. 2011; 109(7):724-8. PMC: 3201702. DOI: 10.1161/CIRCRESAHA.111.253286. View

19.

Ibrahim A, Cheng K, Marban E . Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014; 2(5):606-19. PMC: 4050492. DOI: 10.1016/j.stemcr.2014.04.006. View

20.

Kervadec A, Bellamy V, El Harane N, Arakelian L, Vanneaux V, Cacciapuoti I . Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure. J Heart Lung Transplant. 2016; 35(6):795-807. DOI: 10.1016/j.healun.2016.01.013. View