干细胞外泌体在心血管疾病病理生理学中的作用
- 作者: Rudoy A.S.1, Moskalev A.V.2
-
隶属关系:
- Institute of Physiology of the National Academy of Sciences of Belarus
- Kirov Military Medical Academy
- 期: 卷 26, 编号 1 (2024)
- 页面: 113-128
- 栏目: Review
- URL: https://journals.rcsi.science/1682-7392/article/view/255221
- DOI: https://doi.org/10.17816/brmma595914
- ID: 255221
如何引用文章
详细
本文讨论了细胞外囊泡的治疗潜力现状,这取决于囊泡的分离方法、囊泡的组成以及囊泡和非囊泡成分的特征。众所周知,心肌损伤,尤其是急性心肌梗塞会导致心肌细胞和肌节不可逆转地死亡,并最终导致心力衰竭。成人心脏的再生能力有限,因此,利用细胞疗法激发内源性修复和再生潜能具有潜在的前景。在这种情况下,在受损心肌中注射干细胞和祖细胞的好处是由它们分泌的因子介导的。特别是外泌体,这种源自内泌体的纳米级分泌型细胞外囊泡已成为细胞间通信的关键信号细胞器,现在被认为是干细胞和祖细胞分泌组的关键再生成分。从心脏胚胎干细胞和间充质干细胞、常住干细胞和祖细胞(包括特定的心球细胞亚群)、诱导多能干细胞以及从中分离出来的心肌细胞释放的外泌体具有心脏保护、免疫调节和修复能力。外泌体的另一个很有前景的应用领域是它们在类脂纳米容器和细胞外泡中的靶向药物转运中的应用。由于人工药物载体(包括脂质体和脂基纳米颗粒)受到潜在毒性、免疫原性和无法靶向特定器官的限制,外泌体很有希望成为潜在的药物载体。化合物既可以在外泌体内部运输,也可以在其表面运输。一般来说,分泌的细胞外囊泡,尤其是外泌体,可被视为干细胞,特别是心源性祖细胞(间充质干细胞、内源性心源性祖细胞、心球、胚胎骨髓干细胞、诱导多能骨髓干细胞)分泌组的关键功能成分。在心血管病理研究的临床前模型中,这些细胞已显示出治疗效果。
作者简介
Andrei S. Rudoy
Institute of Physiology of the National Academy of Sciences of Belarus
Email: andrew_rudoy@mail.ru
ORCID iD: 0000-0001-9010-0264
SPIN 代码: 9508-1330
MD, Dr. Sci. (Med.), professor
白俄罗斯, MinskAlexander V. Moskalev
Kirov Military Medical Academy
编辑信件的主要联系方式.
Email: alexmav195223@yandex.ru
ORCID iD: 0009-0004-5659-7464
SPIN 代码: 8227-2647
MD, Dr. Sci. (Med.), professor
俄罗斯联邦, Saint Petersburg参考
- Lázár E, Sadek HA, Bergmann O. Cardiomyocyte renewal in the human heart: insights from the fall-out. Eur Heart J. 2017;38(30):2333–2342. doi: 10.1093/eurheartj/ehx343
- Nguyen PK, Rhee J-W, Wu JC. Adult stem cell therapy and heart failure, 2000 to 2016: a systematic review. JAMA Cardiol. 2016;1(7):831–841. doi: 10.1001/jamacardio.2016.2225
- Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410(6829):701–705. doi: 10.1038/35070587
- Balsam LB, Wagers AJ, Christensen JL, et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature. 2004;428(6983):668–673. doi: 10.1038/nature02460
- Tompkins BA, Balkan W, Winkler J, et al. Preclinical studies of stem cell therapy for heart disease. Circ Res. 2018;122(70): 1006–1020. doi: 10.1161/CIRCRESAHA.117.312486
- Dergilev KV, Vasilets ID, Tsokolaeva ZI, et al. Perspectives of cell therapy for myocardial infarction and heart failure based on cardiosphere cells. Therapeutic archive. 2020;92(4):111–120. EDN: BCFIOG doi: 10.26442/00403660.2020.04.000634
- Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379(9819):895–904. doi: 10.1016/S0140-6736(12)60195-0
- Tarui S, Ishigami S, Ousaka D, et al. Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow up of the Transcoronary Infusion of Cardiac Progenitor Cells in patients with single-ventricle physiology (TICAP) trial. J Thorac Cardiovasc Surg. 2015;150(5):1198–1208.e2. doi: 10.1016/j.jtcvs.2015.06.076
- Ishigami S, Ohtsuki S, Eitoku T, et al. Intracoronary cardiac progenitor cells in single ventricle physiology: the PERSEUS (cardiac progenitor cell infusion to treat univentricular heart disease) randomized phase 2 trial. Circ Res. 2017;120(7):1162–1173. doi: 10.1161/CIRCRESAHA.116.310253
- Chakravarty T, Makkar RR, Ascheim DD, et al. ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: rationale and design. Cell Transplant. 2017;26(2):205–214. doi: 10.3727/096368916X692933
- Chakravarty T, Makkar R, Henry T, et al. Multivessel intracoronary infusion of allogeneic derived cardiosphere cells in cardiomyopathy: long term outcomes of the dilated cardiomyopathy intervention with allogeneic myocardially regenerative cells (DYNAMIC STUDY). J Am Coll Cardiol. 2016;68(18-1):B332. doi: 10.1016/j.jacc.2016.09.848
- Taylor M, Jefferies J, Byrne B, et al. Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial. Neurology. 2019;92(8):866–878. doi: 10.1212/WNL.0000000000006950
- Keerthikumar S, Chisanga D, Ariyaratne D, et al. ExoCarta: a web-based compendium of exosomal cargo. J Mol Biol. 2016;428(4): 688–692. doi: 10.1016/j.jmb.2015.09.019
- Kalra H, Simpson RJ, Hong J, et al. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012;10(12):1001450. doi: 10.1371/journal.pbio.1001450
- Kim D-K, Kang B, Kim OY, et al. EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. J Extracell Vesicles. 2013;2(1):20384. doi: 10.3402/jev.v2i0.20384
- Banerjee MN, Bolli R, Hare JM. Clinical studies of cell therapy in cardiovascular medicine: Recent developments and future directions. Circ Res. 2018;123(2):266–287. doi: 10.1161/CIRCRESAHA.118.311217
- Tang X-L, Li Q, Rokosh G, et al. Long-term outcome of administration of c-kitPOS cardiac progenitor cells after acute myocardial infarction: transplanted cells do not become cardiomyocytes, but structural and functional improvement and proliferation of endogenous cells persist for at least one year. Circ Res. 2016;118(7):1091–1105. doi: 10.1161/CIRCRESAHA.115.307647
- Ibrahim A, Marbán E. Exosomes: fundamental biology and roles in cardiovascular physiology. Ann Rev Physiol. 2016;78:67–83. doi: 10.1146/annurev-physiol-021115-104929
- Zhang ZG, Buller B, Chopp M. Exosomes – beyond stem cells for restorative therapy in stroke and neurological injury. Nat Rev Neurol. 2019;15(4):193–203. doi: 10.1038/s41582-018-0126-4
- Balbi C, Vassalli G. Exosomes: Beyond stem cells for cardiac protection and repair. Stem Cells. 2020;38(11):1387–1399. doi: 10.1002/stem.3261
- Glembotski CC. Expanding the paracrine hypothesis of stem cell–mediated repair in the heart: When the unconventional becomes conventional. Circ Res. 2017;120(5):772–774. doi: 10.1161/CIRCRESAHA.116.310298
- Théry C, Witwer K, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. doi: 10.1080/20013078.2018.1535750
- Van Deun J, Mestdagh P, Agostinis P, et al. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research. Nat Methods. 2017;14(3):228–232. doi: 10.1038/nmeth.4185
- Sluijter JP, Davidson SV, Boulanger CM, et al. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2018;114(1):19–34. doi: 10.1093/cvr/cvx211
- Das S, Ansel KM, Bitzer M, et al. The extracellular RNA communication consortium: establishing foundational knowledge and technologies for extracellular RNA research. Cell. 2019;177(2): 231–242. doi: 10.1016/j.cell.2019.03.023
- Patel GK, Khan MA, Zubair H, et al. Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Sci Rep. 2019;9(1):5335. doi: 10.1038/s41598-019-41800-2
- Gámez-Valero A, Monguió-Tortajada M, Carreras-Planella L, et al. Size-exclusion chromatography-based isolation minimally alters extracellular vesicles’ characteristics compared to precipitating agents. Sci Rep. 2016;6(1):33641. doi: 10.1038/srep33641
- Mol EA, Goumans MJ, Doevendans PA, et al. Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation. Nanomedicine: Nanotechnology, Biology and Medicine. 2017;13(6):2061–2065. doi: 10.1016/j.nano.2017.03.011
- Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell. 2019;177(2):428–445.e18. doi: 10.1016/j.cell.2019.02.029
- Zhang H, Freitas D, Kim HS, et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol. 2018;20(3):332–343. doi: 10.1038/s41556-018-0040-4
- Pluchino S, Smith JA. Explicating exosomes: reclassifying the rising stars of intercellular communication. Cell. 2019;177(2): 225–227. doi: 10.1016/j.cell.2019.03.020
- Mironova OI, Berdysheva MV, Elfimova EM. MicroRNA: a clinician’s view of the state of the problem. Part 1. History of the issue. Eurasian heart journal. 2023;(1):100–107. EDN: TLEZJR doi: 10.38109/2225-1685-2023-1-100-107
- Barile L, Cervio E, Lionetti V, et al. Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A. Cardiovasc Res. 2018;114(7):992–1005. doi: 10.1093/cvr/cvy055
- Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659. doi: 10.1038/ncb1596
- Gupta S, Knowlton AA. HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol. 2007;292(6):H3052–H3056. doi: 10.1152/ajpheart.01355.2006
- Bang C, Batkai S, Dangwal S, et al. Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Investig. 2014;124(5):2136–2146. doi: 10.1172/JCI70577
- Wang X, Huang W, Liu G, et al. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol. 2014;74:139–150. doi: 10.1016/j.yjmcc.2014.05.001
- Cheng M, Yang J, Zhao X, et al. Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells. Nat Commun. 2019;10:959. doi: 10.1038/s41467-019-08895-7
- Loyer X, Zlatanova I, Devue C, et al. Intra-cardiac release of extracellular vesicles shapes inflammation following myocardial infarction. Circ Res. 2018;123(1):100–106. doi: 10.1161/CIRCRESAHA.117.311326
- Biemmi V, Milano G, Ciullo A, et al. Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation. Theranostics. 2020;10(6):2773. doi: 10.7150/thno.39072
- Elahi FM, Farwell DG, Nolta JA, et al. Preclinical translation of exosomes derived from mesenchymal stem/stromal cells. Stem Cells. 2020;38(1):15–21. doi: 10.1002/stem.3061
- Yu H, Wang Z. Cardiomyocyte-derived exosomes: biological functions and potential therapeutic implications. Front. Physiol. 2019;10:1049. doi: 10.3389/fphys.2019.01049
- Ibrahim AG-E, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Rep. 2014;2(5):606–619. doi: 10.1016/j.stemcr.2014.04.006
- Gallet R, Dawkins J, Luthringer D, et al. Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction. Eur Heart J. 2017;38(3):201–211. doi: 10.1093/eurheartj/ehw240
- Kervadec A, Bellamy VE, El Harane N, et al. 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
- Milano G, Biemmi V, Lazzarini E, et al. Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity. Cardiovasc Res. 2020;116(2):383–392. doi: 10.1093/cvr/cvz108
- Vrijsen KR, Maring JA, Chamuleau SA, et al. Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN. Adv Health Mater. 2016;5(19):2555–2565. doi: 10.1002/adhm.201600308
- Tseliou E, Fouad J, Reich H, et al. Fibroblasts rendered antifibrotic, antiapoptotic, and angiogenic by priming with cardiosphere-derived extracellular membrane vesicles. J Am Coll Cardiol. 2015;66(6): 599–611. doi: 10.1016/j.jacc.2015.05.068
- Cambier LY, de Couto G, Ibrahim A, et al. RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL-10 expression and secretion. EMBO Mol Med. 2017;9(3):337–352. doi: 10.15252/emmm.201606924
- Aminzadeh MA, Rogers RG, Fournier M, et al. Exosome-mediated benefits of cell therapy in mouse and human models of Duchenne muscular dystrophy. Stem Cell Rep. 2018;10(3):942–955. doi: 10.1016/j.stemcr.2018.01.023
- Khan M, Nickoloff E, Abramova T, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ Res. 2015;117(1):52–64. doi: 10.1161/CIRCRESAHA.117.305990
- Wang Y, Zhang L, Li Y, et al. Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol. 2015;192:61–69. doi: 10.1016/j.ijcard.2015.05.020
- Bobis-Wozowicz S, Kmiotek K, Sekula M, et al. Human induced pluripotent stem cell-derived microvesicles transmit RNAs and proteins to recipient mature heart cells modulating cell fate and behavior. Stem Cells. 2015;33(9):2748–2761. doi: 10.1002/stem.2078
- Lee WH, Chen W-Y, Shao N-Y, et al. Comparison of non-coding RNAs in exosomes and functional efficacy of human embryonic stem cell-versus induced pluripotent stem cell-derived cardiomyocytes. Stem Cells. 2017;35(10):2138–2149. doi: 10.1002/stem.2669
- Kenneweg F, Bang C, Xiao K, et al. Long noncoding RNA-enriched vesicles secreted by hypoxic cardiomyocytes drive cardiac fibrosis. Mol Ther Nucleic Acids. 2019;18:363–374. doi: 10.1016/j.omtn.2019.09.003
- Agarwal U, George A, Bhutani S, et al. Experimental, systems, and computational approaches to understanding the microRNA-mediated reparative potential of cardiac progenitor cell–derived exosomes from pediatric patients. Circ Res. 2017;120(4):701–712. doi: 10.1161/CIRCRESAHA.116.309935
- Qiao L, Hu S, Zhang H, et al. microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. J Clin Investig. 2019;129(6):2237–2250. doi: 10.1172/JCI123135
- Davidson SM, Riquelme JA, Takov K, et al. Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non-diabetic exosomes in vitro. J Cell Mol Med. 2018;22(1):141–151. doi: 10.1111 /jcmm.13302
- Kim H, Yun N, Mun D, et al. Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes. Biochem Biophys Res Commun. 2018;499(4):803–808. doi: 10.1016/j.bbrc.2018.03.227
- Ciullo A, Biemmi V, Milano G, et al. Exosomal expression of CXCR4 targets cardioprotective vesicles to myocardial infarction and improves outcome after systemic administration. Int J Mol Sci. 2019;20(3):468. doi: 10.3390/ijms20030468
- Cheng Y, Zeng Q, Han Q, et al. Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes. Protein Cell. 2019;10(4):295–299. doi: 10.1007/s13238-018-0529-4
- Sokolov AV, Kostin NN, Ovchinnikova LA, et al. Targeted drug delivery in lipid-like nanocages and extracellular vesicles. Acta Naturae. 2019;11(2):28–41. EDN: XDCTRD doi: 10.32607/20758251-2019-11-2-28-41
- Bunggulawa EJ, Wang W, Yin T, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnol. 2018;16:81. doi: 10.1186/s12951-018-0403-9
- Sawada S-I, Sato YT, Kawasaki R, et al. Nanogel hybrid assembly for exosome intracellular delivery: Effects on endocytosis and fusion by exosome surface polymer engineering. Biomater Sci. 2020;8: 619–630. doi: 10.1039/c9bm01232j
- Sedykh SE, Timofeeva AM, Kuleshova AE, Nevinskiy GA. Milk exosomes as delivery agents for therapy of cancer diseases. Advances in Molecular Oncology. 2022;9(2):23–31. EDN: XOBUYO doi: 10.17650/2313-805X-2022-9-2-23-31
- Andriolo G, Provasi E, Lo Cicero V, et al. Exosomes from human cardiac progenitor cells for therapeutic applications: development of a GMP-grade manufacturing method. Front Physiol. 2018;9:1169. doi: 10.3389/fphys.2018.01169
- Matsumoto A, Takahashi Y, Chang H-Y, et al. Blood concentrations of small extracellular vesicles are determined by a balance between abundant secretion and rapid clearance. J Extracell Vesicles. 2020;9(1):1696517. doi: 10.1080/20013078.2019.1696517