Cardiac progenitor cell therapy: mechanisms of action.
Adult cardiac progenitor cells
Cardiac regeneration
Exosomes
Non-coding RNAs
Journal
Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195
Informations de publication
Date de publication:
05 Mar 2024
05 Mar 2024
Historique:
received:
01
07
2023
accepted:
17
02
2024
medline:
6
3
2024
pubmed:
6
3
2024
entrez:
5
3
2024
Statut:
epublish
Résumé
Heart failure (HF) is an end-stage of many cardiac diseases and one of the main causes of death worldwide. The current management of this disease remains suboptimal. The adult mammalian heart was considered a post-mitotic organ. However, several reports suggest that it may possess modest regenerative potential. Adult cardiac progenitor cells (CPCs), the main players in the cardiac regeneration, constitute, as it may seem, a heterogenous group of cells, which remain quiescent in physiological conditions and become activated after an injury, contributing to cardiomyocytes renewal. They can mediate their beneficial effects through direct differentiation into cardiac cells and activation of resident stem cells but majorly do so through paracrine release of factors. CPCs can secrete cytokines, chemokines, and growth factors as well as exosomes, rich in proteins, lipids and non-coding RNAs, such as miRNAs and YRNAs, which contribute to reparation of myocardium by promoting angiogenesis, cardioprotection, cardiomyogenesis, anti-fibrotic activity, and by immune modulation. Preclinical studies assessing cardiac progenitor cells and cardiac progenitor cells-derived exosomes on damaged myocardium show that administration of cardiac progenitor cells-derived exosomes can mimic effects of cell transplantation. Exosomes may become new promising therapeutic strategy for heart regeneration nevertheless there are still several limitations as to their use in the clinic. Key questions regarding their dosage, safety, specificity, pharmacokinetics, pharmacodynamics and route of administration remain outstanding. There are still gaps in the knowledge on basic biology of exosomes and filling them will bring as closer to translation into clinic.
Identifiants
pubmed: 38444042
doi: 10.1186/s13578-024-01211-x
pii: 10.1186/s13578-024-01211-x
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
30Informations de copyright
© 2024. The Author(s).
Références
Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385(9970):812–24. https://doi.org/10.1016/s0140-6736(14)61889-4 .
doi: 10.1016/s0140-6736(14)61889-4
pubmed: 25467564
Yancy CW, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA Guideline for the management of Heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines and the heart failure society of Amer. Circulation. 2016;134(13). https://doi.org/10.1161/CIR.0000000000000509 .
Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. Jun. 2016;13(6):368–78. https://doi.org/10.1038/nrcardio.2016.25 .
Shah KS, et al. Heart failure with preserved, Borderline, and reduced ejection fraction. J Am Coll Cardiol. 2017;70(20):2476–86. https://doi.org/10.1016/j.jacc.2017.08.074 .
doi: 10.1016/j.jacc.2017.08.074
pubmed: 29141781
Virani SS, et al. Heart Disease and Stroke Statistics—2023 update: a Report from the American Heart Association. Circulation. 2021;148(4). https://doi.org/10.1161/CIR.0000000000000950 .
Yancy CW, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16). https://doi.org/10.1161/CIR.0b013e31829e8776 .
Urbich M et al. Nov., A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014–2020), Pharmacoeconomics, vol. 38, no. 11, pp. 1219–1236, 2020, https://doi.org/10.1007/s40273-020-00952-0 .
McDonagh TA, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;43(6):440–1. https://doi.org/10.1093/eurheartj/ehab368 .
doi: 10.1093/eurheartj/ehab368
Miller L, Birks E, Guglin M, Lamba H, Frazier OH. Use of Ventricular Assist devices and Heart Transplantation for Advanced Heart failure. Circ Res. 2019;124(11):1658–78. https://doi.org/10.1161/circresaha.119.313574 .
doi: 10.1161/circresaha.119.313574
pubmed: 31120817
Ilieșiu AM, Hodorogea AS. Treatment of Heart failure with preserved ejection fraction. Advances in Experimental Medicine and Biology. Springer International Publishing; 2018. pp. 67–87. https://doi.org/10.1007/5584_2018_149 .
Chung JS, Emerson D, Megna D, Arabia FA. Total artificial heart: surgical technique in the patient with normal cardiac anatomy, Ann. Cardiothorac. Surg, vol. 9, no. 2, pp. 818–888, Mar. 2020, https://doi.org/10.21037/ACS.2020.02.09 .
Henn MC, Mokadam NA. Total artificial heart as a bridge to transplantation, Curr. Opin. Organ Transplant, vol. 27, no. 3, pp. 222–228, Jun. 2022, https://doi.org/10.1097/MOT.0000000000000982 .
Chen Q, et al. Heart transplantation after total artificial heart bridging-outcomes over 15 years. Clin Transpl. Nov. 2022;36(11). https://doi.org/10.1111/CTR.14781 .
Olson EN, Schneider MD. Sizing up the heart: development redux in disease. Genes Dev. 2003;17(16):1937–56. https://doi.org/10.1101/gad.1110103 .
doi: 10.1101/gad.1110103
pubmed: 12893779
Tam SKC, Gu W, Mahdavi V, Nadal-Ginard B. Cardiac myocyte terminal differentiation. Ann N Y Acad Sci. 1995;752(1):72–9. https://doi.org/10.1111/j.1749-6632.1995.tb17407.x .
doi: 10.1111/j.1749-6632.1995.tb17407.x
pubmed: 7755297
Bergmann O, et al. Evidence for cardiomyocyte renewal in humans. Science. Apr. 2009;324(5923):98–102. https://doi.org/10.1126/science.1164680 .
Hsieh PCH et al. Aug., Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury, Nat. Med, vol. 13, no. 8, pp. 970–974, 2007, https://doi.org/10.1038/nm1618 .
Hsueh Y-C, Wu JMF, Yu C-K, Wu KK, Hsieh PCH. Prostaglandin E
Walsh S, Pontén A, Fleischmann BK, Jovinge S. Cardiomyocyte cell cycle control and growth estimation in vivo—an analysis based on cardiomyocyte nuclei. Cardiovasc Res. 2010;86(3):365–73. https://doi.org/10.1093/cvr/cvq005 .
doi: 10.1093/cvr/cvq005
pubmed: 20071355
Nadal-Ginard B, Ellison GM, Torella D. The cardiac stem cell compartment is indispensable for myocardial cell homeostasis, repair and regeneration in the adult. Stem Cell Res. 2014;13(3):615–30. https://doi.org/10.1016/j.scr.2014.04.008 .
doi: 10.1016/j.scr.2014.04.008
pubmed: 24838077
Bergmann O, et al. Dynamics of cell generation and turnover in the Human Heart. Cell. 2015;161(7):1566–75. https://doi.org/10.1016/j.cell.2015.05.026 .
doi: 10.1016/j.cell.2015.05.026
pubmed: 26073943
Senyo SE, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. Jan. 2013;493(7432):433–6. https://doi.org/10.1038/nature11682 .
Malliaras K et al. Feb., Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart, EMBO Mol. Med, vol. 5, no. 2, pp. 191–209, 2013, https://doi.org/10.1002/emmm.201201737 .
Scalise M, et al. Heterogeneity of adult cardiac stem cells. Advances in Experimental Medicine and Biology. Springer International Publishing; 2019. pp. 141–78. https://doi.org/10.1007/978-3-030-24108-7_8 .
Beltrami AP, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. Sep. 2003;114(6):763–76. https://doi.org/10.1016/S0092-8674(03)00687-1 .
Kanazawa H et al. Mar., Cellular postconditioning: allogeneic cardiosphere-derived cells reduce infarct size and attenuate microvascular obstruction when administered after reperfusion in pigs with acute myocardial infarction, Circ. Heart Fail, vol. 8, no. 2, pp. 322–332, 2015, https://doi.org/10.1161/CIRCHEARTFAILURE.114.001484 .
Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res. Feb. 2003;92(2):139–50. https://doi.org/10.1161/01.RES.0000053618.86362.DF .
Wang L, et al. Role of cardiac progenitor cell-derived exosome‐mediated microRNA‐210 in cardiovascular disease. J Cell Mol Med. Nov. 2019;23(11):7124. https://doi.org/10.1111/JCMM.14562 .
Le T, Chong J. Cardiac progenitor cells for heart repair. Cell Death Discov. Jul. 2016;2:16052. https://doi.org/10.1038/cddiscovery.2016.52 .
Ge Z, Lal S, Le TYL, Dos Remedios C, Chong JJH. Cardiac stem cells: translation to human studies, Biophys. Rev, vol. 7, no. 1, pp. 127–139, Mar. 2015, https://doi.org/10.1007/s12551-014-0148-0 .
Smith AJ, et al. Isolation and characterization of resident endogenous c-Kit + cardiac stem cells from the adult mouse and rat heart. Nat Protoc. 2014;9(7):1662–81. https://doi.org/10.1038/nprot.2014.113 .
doi: 10.1038/nprot.2014.113
pubmed: 24945383
Fransioli J, et al. Evolution of the c-kit-positive cell response to pathological challenge in the myocardium. Stem Cells. May 2008;26(5):1315–24. https://doi.org/10.1634/stemcells.2007-0751 .
Kawaguchi N et al. Dec., c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling, PLoS One, vol. 5, no. 12, pp. e14297–e14297, 2010, https://doi.org/10.1371/journal.pone.0014297 .
Kulandavelu S, et al. Pim1 kinase overexpression enhances ckit + cardiac stem cell Cardiac Repair following myocardial infarction in Swine. J Am Coll Cardiol. Dec. 2016;68(22):2454–64. https://doi.org/10.1016/J.JACC.2016.09.925 .
Lee ST et al. Jan., Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction, J. Am. Coll. Cardiol, vol. 57, no. 4, pp. 455–465, 2011, https://doi.org/10.1016/J.JACC.2010.07.049 .
Malliaras K, et al. Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation. Jan. 2012;125(1):100–12. https://doi.org/10.1161/CIRCULATIONAHA.111.042598 .
Tseliou E, et al. Allogeneic cardiospheres safely boost cardiac function and attenuate adverse remodeling after myocardial infarction in immunologically mismatched rat strains. J Am Coll Cardiol. 2013;61(10):1108–19. https://doi.org/10.1016/J.JACC.2012.10.052 .
doi: 10.1016/J.JACC.2012.10.052
pubmed: 23352785
Malliaras K et al. Dec., Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction, Circulation, vol. 128, no. 25, pp. 2764–2775, 2013, https://doi.org/10.1161/CIRCULATIONAHA.113.002863 .
Williams AR et al. Jan., Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction, Circulation, vol. 127, no. 2, pp. 213–223, 2013, https://doi.org/10.1161/CIRCULATIONAHA.112.131110 .
Bolli R et al. Jul., Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy, Circulation, vol. 128, no. 2, pp. 122–131, 2013, https://doi.org/10.1161/CIRCULATIONAHA.112.001075 .
Welt FGP, et al. Effect of cardiac stem cells on left-ventricular remodeling in a canine model of chronic myocardial infarction. Circ Heart Fail. Jan. 2013;6(1):99–106. https://doi.org/10.1161/CIRCHEARTFAILURE.112.972273 .
Bolli R, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet (London England). 2011;378:1847–57. https://doi.org/10.1016/S0140-6736(11)61590-0 .
doi: 10.1016/S0140-6736(11)61590-0
pubmed: 22088800
Editors TL. Retraction-cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet (London England). Mar. 2019;393:1084. https://doi.org/10.1016/S0140-6736(19)30542-2 .
Liu Q, et al. Genetic lineage tracing identifies in situ kit-expressing cardiomyocytes. Cell Res. Jan. 2016;26(1):119–30. https://doi.org/10.1038/cr.2015.143 .
Sultana N, et al. Resident c-kit(+) cells in the heart are not cardiac stem cells. Nat Commun. Oct. 2015;6:8701. https://doi.org/10.1038/ncomms9701 .
van Berlo JH, et al. c-kit + cells minimally contribute cardiomyocytes to the heart. Nature. May 2014;509(7500):337–41. https://doi.org/10.1038/nature13309 .
Vicinanza C et al. Dec., Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification, Cell Death Differ, vol. 24, no. 12, pp. 2101–2116, 2017, https://doi.org/10.1038/cdd.2017.130 .
Messina E, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95(9):911–21. https://doi.org/10.1161/01.res.0000147315.71699.51 .
doi: 10.1161/01.res.0000147315.71699.51
pubmed: 15472116
Smith RR, et al. Regenerative potential of Cardiosphere-Derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115(7):896–908. https://doi.org/10.1161/circulationaha.106.655209 .
doi: 10.1161/circulationaha.106.655209
pubmed: 17283259
Makkar RR, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet (London England). Mar. 2012;379:895–904. https://doi.org/10.1016/S0140-6736(12)60195-0 .
Malliaras K, et al. Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol. Jan. 2014;63(2):110–22. https://doi.org/10.1016/J.JACC.2013.08.724 .
Chugh AR, et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. Sep. 2012;126(11 Suppl 1). https://doi.org/10.1161/CIRCULATIONAHA.112.092627 .
Ishigami S, et al. Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Circ Res. Feb. 2015;116(4):653–64. https://doi.org/10.1161/CIRCRESAHA.116.304671 .
Makkar RR et al. Sep., Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial, Eur. Heart J, vol. 41, no. 36, pp. 3451–3458, 2020, https://doi.org/10.1093/EURHEARTJ/EHAA541 .
Ishigami S et al. Mar., 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, vol. 120, no. 7, pp. 1162–1173, 2017, https://doi.org/10.1161/CIRCRESAHA.116.310253 .
Sano T et al. Mar., Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease, Circ. Res, vol. 122, no. 7, pp. 994–1005, 2018, https://doi.org/10.1161/CIRCRESAHA.117.312311 .
Menasché P, et al. Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular progenitors for severe ischemic left ventricular dysfunction. J Am Coll Cardiol. Jan. 2018;71(4):429–38. https://doi.org/10.1016/J.JACC.2017.11.047 .
Sanz-Ruiz R et al. Jun., Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction), Circ. Res, vol. 121, no. 1, pp. 71–80, 2017, https://doi.org/10.1161/CIRCRESAHA.117.310651 .
Fernández-Avilés F, et al. Safety and Efficacy of Intracoronary infusion of Allogeneic Human Cardiac Stem cells in patients with ST-Segment Elevation myocardial infarction and left ventricular dysfunction. Circ Res. 2018;123(5):579–89. https://doi.org/10.1161/CIRCRESAHA.118.312823 .
doi: 10.1161/CIRCRESAHA.118.312823
pubmed: 29921651
Bolli R et al. Apr., A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial, Eur. J. Heart Fail, vol. 23, no. 4, pp. 661–674, 2021, https://doi.org/10.1002/EJHF.2178 .
Taylor M et al. Feb., Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial, Neurology, vol. 92, no. 8, pp. E866–E878, 2019, https://doi.org/10.1212/WNL.0000000000006950 .
Hirai K, et al. Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy. Sci Transl Med. Dec. 2020;12(573). https://doi.org/10.1126/SCITRANSLMED.ABB3336 .
Li X-H et al. Dec., Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction, Stem Cells Transl. Med, vol. 4, no. 12, pp. 1415–1424, 2015, https://doi.org/10.5966/SCTM.2015-0136 .
Nsair A, et al. Characterization and therapeutic potential of Induced Pluripotent Stem Cell-Derived Cardiovascular Progenitor cells. PLoS ONE. Oct. 2012;7(10). https://doi.org/10.1371/JOURNAL.PONE.0045603 .
Birket MJ, Mummery CL. Pluripotent stem cell derived cardiovascular progenitors – A developmental perspective, Dev. Biol, vol. 400, no. 2, pp. 169–179, Apr. 2015, https://doi.org/10.1016/J.YDBIO.2015.01.012 .
Takahashi K et al. Nov., Induction of pluripotent stem cells from adult human fibroblasts by defined factors, Cell, vol. 131, no. 5, pp. 861–872, 2007, https://doi.org/10.1016/J.CELL.2007.11.019 .
Lian X, et al. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc. Jan. 2013;8(1):162–75. https://doi.org/10.1038/NPROT.2012.150 .
Olmer R et al. Jul., Long term expansion of undifferentiated human iPS and ES cells in suspension culture using a defined medium, Stem Cell Res, vol. 5, no. 1, pp. 51–64, 2010, https://doi.org/10.1016/J.SCR.2010.03.005 .
Moretti A et al. Dec., Multipotent Embryonic Isl1 + Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification, Cell, vol. 127, no. 6, pp. 1151–1165, 2006, https://doi.org/10.1016/J.CELL.2006.10.029 .
Kattman SJ, Huber TL, Keller GMM. Multipotent Flk-1 + Cardiovascular Progenitor Cells Give Rise to the Cardiomyocyte, Endothelial, and Vascular Smooth Muscle Lineages, Dev. Cell, vol. 11, no. 5, pp. 723–732, Nov. 2006, https://doi.org/10.1016/J.DEVCEL.2006.10.002 .
Elliott DA et al. Dec., NKX2-5(eGFP/w) hESCs for isolation of human cardiac progenitors and cardiomyocytes, Nat. Methods, vol. 8, no. 12, pp. 1037–1043, 2011, https://doi.org/10.1038/NMETH.1740 .
Drowley L, et al. Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor cells in phenotypic screening: a transforming growth Factor- β type 1 receptor kinase inhibitor induces efficient Cardiac differentiation. Stem Cells Transl Med. Feb. 2016;5(2):164–74. https://doi.org/10.5966/SCTM.2015-0114/-/DC1 .
Zhou M, et al. Generation of a human iPSC line GIBHi002-A-2 with a dual-reporter for NKX2-5 using TALENs. Stem Cell Res. Jan. 2020;50. https://doi.org/10.1016/J.SCR.2020.102120 .
Malliaras K, Marbán E. Cardiac cell therapy: where we’ve been, where we are, and where we should be headed. Br Med Bull. 2011;98(1):161–85. https://doi.org/10.1093/bmb/ldr018 .
doi: 10.1093/bmb/ldr018
pubmed: 21652595
pmcid: 3149211
Pagano F, et al. The Biological mechanisms of Action of Cardiac Progenitor Cell Therapy. Curr Cardiol Rep. 2018;20(10). https://doi.org/10.1007/s11886-018-1031-6 .
Chimenti I et al. Mar., Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice, Circ. Res, vol. 106, no. 5, pp. 971–980, 2010, https://doi.org/10.1161/CIRCRESAHA.109.210682 .
Stastna M, Chimenti I, Marbán E, Van Eyk JE. Identification and functionality of proteomes secreted by rat cardiac stem cells and neonatal cardiomyocytes, Proteomics, vol. 10, no. 2, pp. 245–253, Jan. 2010, https://doi.org/10.1002/pmic.200900515 .
Sharma S et al. Mar., A Deep Proteome Analysis Identifies the Complete Secretome as the Functional Unit of Human Cardiac Progenitor Cells, Circ. Res, vol. 120, no. 5, pp. 816–834, 2017, https://doi.org/10.1161/CIRCRESAHA.116.309782 .
Malliaras K et al. Jun., Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction, EMBO Mol. Med, vol. 6, no. 6, pp. 760–777, 2014, https://doi.org/10.1002/emmm.201303626 .
Cheng K, et al. Human cardiosphere-derived cells from advanced heart failure patients exhibit augmented functional potency in myocardial repair. JACC Heart Fail. Feb. 2014;2(1):49–61. https://doi.org/10.1016/j.jchf.2013.08.008 .
Tilokee EL, et al. Paracrine Engineering of Human explant-derived cardiac stem cells to over-express stromal-cell derived factor 1α enhances myocardial repair. Stem Cells. 2016;34(7):1826–35. https://doi.org/10.1002/stem.2373 .
doi: 10.1002/stem.2373
pubmed: 27059540
Mayfield AE et al. Oct., Interleukin-6 Mediates Post-Infarct Repair by Cardiac Explant-Derived Stem Cells, Theranostics, vol. 7, no. 19, pp. 4850–4861, 2017, https://doi.org/10.7150/thno.19435 .
Torán JL, et al. CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome. Sci Rep. Oct. 2017;7(1):12490. https://doi.org/10.1038/s41598-017-11976-6 .
Jackson R, et al. Paracrine Engineering of Human Cardiac Stem cells with insulin-like Growth factor 1 enhances myocardial repair. J Am Heart Assoc. Sep. 2015;4(9):e002104–4. https://doi.org/10.1161/JAHA.115.002104 .
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. Feb. 2020;367:eaau6977. https://doi.org/10.1126/science.aau6977 . no. 6478.
Cambria E, et al. Translational cardiac stem cell therapy: advancing from first-generation to next-generation cell types. NPJ Regen Med. Jun. 2017;2(1). https://doi.org/10.1038/S41536-017-0024-1 .
Barile L, Gherghiceanu M, Popescu LM, Moccetti T, Vassalli G. Ultrastructural evidence of Exosome Secretion by Progenitor cells in adult mouse myocardium and adult human cardiospheres. J Biomed Biotechnol. 2012;2012. https://doi.org/10.1155/2012/354605 .
Manole CG, Cismaşiu V, Gherghiceanu M, Popescu LM. Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis. J Cell Mol Med. Nov. 2011;15(11):2284–96. https://doi.org/10.1111/J.1582-4934.2011.01449.X .
Barile L et al. Sep., Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction, Cardiovasc. Res, vol. 103, no. 4, pp. 530–541, 2014, https://doi.org/10.1093/CVR/CVU167 .
Ibrahim AG-E, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem cell Rep. May 2014;2(5):606–19. https://doi.org/10.1016/j.stemcr.2014.04.006 .
Gallet R et al. Jan., Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction, Eur. Heart J, vol. 38, no. 3, pp. 201–211, 2017, https://doi.org/10.1093/EURHEARTJ/EHW240 .
Tseliou E, et al. Fibroblasts rendered Antifibrotic, Antiapoptotic, and angiogenic by priming with Cardiosphere-Derived Extracellular membrane vesicles. J Am Coll Cardiol. Aug. 2015;66(6):599–611. https://doi.org/10.1016/j.jacc.2015.05.068 .
Skotland T, Hessvik NP, Sandvig K, Llorente A. Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology, J. Lipid Res, vol. 60, no. 1, pp. 9–18, Jan. 2019, https://doi.org/10.1194/jlr.R084343 .
van Balkom BWM, Eisele AS, Pegtel DM, Bervoets S, Verhaar MC. Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting. J Extracell Vesicles. May 2015;4:26760. https://doi.org/10.3402/jev.v4.26760 .
Wen SW, et al. Breast Cancer-derived exosomes reflect the cell‐of‐origin phenotype. Proteomics. 2019;19(8). https://doi.org/10.1002/pmic.201800180 .
Barile L, et al. Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A. Cardiovasc Res. 2018;114:992–1005. https://doi.org/10.1093/cvr/cvy055 .
doi: 10.1093/cvr/cvy055
pubmed: 29518183
Bartel DP. MicroRNAs. Cell. 2004;116(2):281–97. https://doi.org/10.1016/s0092-8674(04)00045-5 .
doi: 10.1016/s0092-8674(04)00045-5
pubmed: 14744438
Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs, Genome Res, vol. 19, no. 1, pp. 92–105, Jan. 2009, https://doi.org/10.1101/gr.082701.108 .
Hutter K, et al. SAFB2 enables the Processing of Suboptimal Stem-Loop structures in clustered primary miRNA transcripts. Mol Cell. 2020;78(5):876–89. https://doi.org/10.1016/j.molcel.2020.05.011 .
doi: 10.1016/j.molcel.2020.05.011
pubmed: 32502422
Gagnon KT, Li L, Chu Y, Janowski BA, Corey DR. RNAi factors are present and active in human cell nuclei. Cell Rep. Jan. 2014;6(1):211–21. https://doi.org/10.1016/j.celrep.2013.12.013 .
Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 2015;16:421–33. https://doi.org/10.1038/nrg3965 .
doi: 10.1038/nrg3965
pubmed: 26077373
Espinoza-Lewis RA, Wang D-Z. MicroRNAs in heart development. Curr Top Dev Biol. 2012;100:279–317. https://doi.org/10.1016/B978-0-12-387786-4.00009-9 .
doi: 10.1016/B978-0-12-387786-4.00009-9
pubmed: 22449848
pmcid: 4888772
Kalayinia S, Arjmand F, Maleki M, Malakootian M, Singh CP. MicroRNAs: roles in cardiovascular development and disease. Cardiovasc Pathol. 2021;50:107296. https://doi.org/10.1016/j.carpath.2020.107296 .
doi: 10.1016/j.carpath.2020.107296
pubmed: 33022373
Tang R, Long T, Lui KO, Chen Y, Huang Z-P. A Roadmap for Fixing the Heart: RNA Regulatory Networks in Cardiac Disease, Mol. Ther. Nucleic Acids, vol. 20, pp. 673–686, Jun. 2020, https://doi.org/10.1016/j.omtn.2020.04.007 .
Gray WD et al. Jan., Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology, Circ. Res, vol. 116, no. 2, pp. 255–263, 2015, https://doi.org/10.1161/CIRCRESAHA.116.304360 .
de Couto G, et al. Exosomal MicroRNA transfer into Macrophages mediates Cellular Postconditioning. Circulation. Jul. 2017;136(2):200–14. https://doi.org/10.1161/CIRCULATIONAHA.116.024590 .
Kowalski MP, Krude T. Functional roles of non-coding Y RNAs, Int. J. Biochem. Cell Biol, vol. 66, pp. 20–29, Sep. 2015, https://doi.org/10.1016/j.biocel.2015.07.003 .
Lerner MR, Boyle JA, Hardin JA, Steitz JA. Two Novel Classes of Small Ribonucleoproteins Detected by Antibodies Associated with Lupus Erythematosus, Science (80-.), vol. 211, no. 4480, pp. 400–402, 1981, https://doi.org/10.1126/science.6164096 .
Hendrick JP, Wolin SL, Rinke J, Lerner MR, Steitz JA. Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells, Mol. Cell. Biol, vol. 1, no. 12, pp. 1138–1149, Dec. 1981, https://doi.org/10.1128/mcb.1.12.1138-1149.1981 .
Krude T, Christov CP, Hyrien O, Marheineke K. Y RNA functions at the initiation step of mammalian chromosomal DNA replication. J Cell Sci. 2009;122(16):2836–45. https://doi.org/10.1242/jcs.047563 .
doi: 10.1242/jcs.047563
pubmed: 19657016
Guglas K et al. Aug., YRNAs and YRNA-Derived Fragments as New Players in Cancer Research and Their Potential Role in Diagnostics, Int. J. Mol. Sci, vol. 21, no. 16, p. 5682, 2020, https://doi.org/10.3390/ijms21165682 .
Cambier L, de Couto G, Ibrahim A, Marbán E. Abstract 16009: Y RNA fragments enriched in Exosomes from Cardiosphere-derived cells mediate Cardioprotection and Macrophage polarization. Circulation. 2015;132(suppl3). https://doi.org/10.1161/circ.132.suppl_3.16009 .
Cambier L et al. Mar., Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL-10 expression and secretion, EMBO Mol. Med, vol. 9, no. 3, pp. 337–352, 2017, https://doi.org/10.15252/emmm.201606924 .
Cambier L et al. Angiotensin II-Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment, Hypertens. (Dallas, Tex 1979), vol. 72, no. 2, pp. 370–380, Aug. 2018, https://doi.org/10.1161/HYPERTENSIONAHA.118.11239 .
Huang F et al. Apr., Exosomally derived Y RNA fragment alleviates hypertrophic cardiomyopathy in transgenic mice, Mol. Ther. Nucleic Acids, vol. 24, pp. 951–960, 2021, https://doi.org/10.1016/j.omtn.2021.04.014 .
Chimenti I, Frati G. Cell-derived exosomes for Cardiovascular therapies. Hypertension. 2018;72(2):279–80. https://doi.org/10.1161/hypertensionaha.118.10684 .
doi: 10.1161/hypertensionaha.118.10684
pubmed: 29866741
Kishore R, Khan M. Cardiac cell-derived exosomes: changing face of regenerative biology. Eur Heart J. Jan. 2017;38(3):212–5. https://doi.org/10.1093/eurheartj/ehw324 .
Sluijter JPG, van Rooij E. Exosomal MicroRNA clusters are important for the therapeutic effect of Cardiac Progenitor cells. Circ Res. 2015;116(2):219–21. https://doi.org/10.1161/circresaha.114.305673 .
doi: 10.1161/circresaha.114.305673
pubmed: 25593269
Kishore R, Khan M. More than tiny Sacks: stem cell exosomes as cell-free modality for Cardiac Repair. Circ Res. Jan. 2016;118(2):330–43. https://doi.org/10.1161/CIRCRESAHA.115.307654 .
Diener C, Keller A, Meese E. Emerging concepts of miRNA therapeutics: from cells to clinic. Trends Genet. 2022;38(6):613–26. https://doi.org/10.1016/j.tig.2022.02.006 .
doi: 10.1016/j.tig.2022.02.006
pubmed: 35303998
McKown EN, et al. Impaired adhesion of induced pluripotent stem cell-derived cardiac progenitor cells (iPSC-CPCs) to isolated extracellular matrix from failing hearts. Heliyon. Oct. 2018;4(10):e00870. https://doi.org/10.1016/j.heliyon.2018.e00870 .