Is Cardioprotection Dead?

Circulation

Volumn 136, Issue 1, 2017, Pages 98-109

  Lefer, David J ^a   Marbán, Eduardo ^b  

^a LOUISIANA STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

cardiosphere derived cells; cell and tissue based therapy; heart failure; myocardial Infarction; ventricular function, left

Indexed keywords

ACUTE HEART INFARCTION; CARDIAC STEM CELL; CARDIOSPHERE DERIVED CELL; CELL THERAPY; HEART INFARCTION SIZE; HEART LEFT VENTRICLE FUNCTION; HEART MUSCLE BLOOD FLOW; HEART MUSCLE REPERFUSION; HEART PRESERVATION; HEART PROTECTION; HUMAN; INFLAMMATION; ISCHEMIC POSTCONDITIONING; MACROPHAGE; MYOCARDIAL ISCHEMIA REPERFUSION INJURY; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; BIOLOGICAL THERAPY; CARDIAC MUSCLE CELL; MYOCARDIAL INFARCTION; PATHOLOGY; PROCEDURES; TRANSPLANTATION; TRENDS;

ANIMALS; CELL- AND TISSUE-BASED THERAPY; HUMANS; ISCHEMIC POSTCONDITIONING; MYOCARDIAL INFARCTION; MYOCARDIAL REPERFUSION; MYOCYTES, CARDIAC;

EID: 85021696166     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.116.027039     Document Type: Review

References (102)

1. Gross L, Blum L, Silverman G. Experimental attempts to increase the blood supply to the dog's heart by means of coronary sinus occlusion. J Exp Med. 1937;65:91-108.
2. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13-20. doi: 10.1016/ S0140-6736(03)12113-7.
3. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990;81:1161-1172.
4. St John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moyé LA, Dagenais GR, Lamas GA, Klein M, Sussex B, Goldman S. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation. 1994;89:68-75.
5. Reimer KA, Jennings RB. Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs. Circulation. 1985;71:1069-1075.
6. Gallagher KP, Buda AJ, Pace D, Gerren RA, Shlafer M. Failure of superoxide dismutase and catalase to alter size of infarction in conscious dogs after 3 hours of occlusion followed by reperfusion. Circulation. 1986;73: 1065-1076.
7. Uraizee A, Reimer KA, Murry CE, Jennings RB. Failure of superoxide dismutase to limit size of myocardial infarction after 40 minutes of ischemia and 4 days of reperfusion in dogs. Circulation. 1987;75:1237-1248.
8. Puett DW, Forman MB, Cates CU, Wilson BH, Hande KR, Friesinger GC, Virmani R. Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion. Circulation. 1987;76:678-686.
9. Chatelain P, Latour JG, Tran D, de Lorgeril M, Dupras G, Bourassa M. Neutrophil accumulation in experimental myocardial infarcts: relation with extent of injury and effect of reperfusion. Circulation. 1987;75:1083-1090.
10. Richard VJ, Murry CE, Jennings RB, Reimer KA. Therapy to reduce free radicals during early reperfusion does not limit the size of myocardial infarcts caused by 90 minutes of ischemia in dogs. Circulation. 1988;78:473-480.
11. Tanaka M, Stoler RC, FitzHarris GP, Jennings RB, Reimer KA. Evidence against the "early protection-delayed death" hypothesis of superoxide dismutase therapy in experimental myocardial infarction. Polyethylene glycol-superoxide dismutase plus catalase does not limit myocardial infarct size in dogs. Circ Res. 1990;67:636-644.
12. Tanaka M, Brooks SE, Richard VJ, FitzHarris GP, Stoler RC, Jennings RB, Arfors KE, Reimer KA. Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs. Circulation. 1993;87:526-535.
13. Goldbourt U, Behar S, Reicher-Reiss H, Zion M, Mandelzweig L, Kaplinsky E. Early administration of nifedipine in suspected acute myocardial infarction. The Secondary Prevention Reinfarction Israel Nifedipine Trial 2 Study. Arch Intern Med. 1993;153:345-353.
14. Flaherty JT, Pitt B, Gruber JW, Heuser RR, Rothbaum DA, Burwell LR, George BS, Kereiakes DJ, Deitchman D, Gustafson N. Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation. 1994;89:1982-1991.
15. ESPRIM Group. The ESPRIM trial: short-term treatment of acute myocardial infarction with molsidomine. European Study of Prevention of Infarct with Molsidomine (ESPRIM) Group. Lancet. 1994;344:91-97.
16. Wall TC, Califf RM, Blankenship J, Talley JD, Tannenbaum M, Schwaiger M, Gacioch G, Cohen MD, Sanz M, Leimberger JD. Intravenous Fluosol in the treatment of acute myocardial infarction. Results of the Thrombolysis and Angioplasty in Myocardial Infarction 9 Trial. TAMI 9 Research Group. Circulation. 1994;90:114-120.
17. EMIP-FR Group. Effect of 48-h intravenous trimetazidine on short-and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial. The EMIP-FR Group. European Myocardial Infarction Project - Free Radicals. Eur Heart J. 2000;21:1537-1546.
18. Rusnak JM, Kopecky SL, Clements IP, Gibbons RJ, Holland AE, Peterman HS, Martin JS, Saoud JB, Feldman RL, Breisblatt WM, Simons M, Gessler CJ Jr, Yu AS. An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study). Am J Cardiol. 2001;88:482-487.
19. Zeymer U, Suryapranata H, Monassier JP, Opolski G, Davies J, Rasmanis G, Linssen G, Tebbe U, Schröder R, Tiemann R, Machnig T, Neuhaus KL; ESCAMI Investigators. The Na(+)/H(+) exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial. J Am Coll Cardiol. 2001;38:1644-1650.
20. Bär FW, Tzivoni D, Dirksen MT, Fernández-Ortiz A, Heyndrickx GR, Brachmann J, Reiber JH, Avasthy N, Tatsuno J, Davies M, Hibberd MG, Krucoff MW; CASTEMI Study Group. Results of the first clinical study of adjunctive CAldaret (MCC-135) in patients undergoing primary percutaneous coronary intervention for ST-Elevation Myocardial Infarction: the randomized multicentre CASTEMI study. Eur Heart J. 2006;27:2516-2523. doi: 10.1093/eurheartj/ehl304.
21. Mahaffey KW, Granger CB, Nicolau JC, Ruzyllo W, Weaver WD, Theroux P, Hochman JS, Filloon TG, Mojcik CF, Todaro TG, Armstrong PW; COMPLY Investigators. Effect of pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to fibrinolysis in acute myocardial infarction: the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) trial. Circulation. 2003;108:1176-1183. doi: 10.1161/01. CIR.0000087404.53661.F8.
22. Armstrong PW, Granger CB. Pexelizumab and the APEX AMI trial. JAMA. 2007;297:1881; author reply 1881-1881; author reply 1882. doi: 10.1001/jama.297.17.1881-b.
23. Magnesium in Coronaries (MAGIC) Trial Investigators. Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet. 2002;360:1189-1196.
24. Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, Nagai Y, Nanto S, Watanabe K, Fukuzawa S, Hirayama A, Nakamura N, Kimura K, Fujii K, Ishihara M, Saito Y, Tomoike H, Kitamura S; J-WIND investigators. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet. 2007;370:1483-1493. doi: 10.1016/S0140-6736(07)61634-1.
25. Erlinge D, Götberg M, Lang I, Holzer M, Noc M, Clemmensen P, Jensen U, Metzler B, James S, Bötker HE, Omerovic E, Engblom H, Carlsson M, Arheden H, Ostlund O, Wallentin L, Harnek J, Olivecrona GK. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol. 2014;63:1857-1865. doi: 10.1016/j.jacc.2013.12.027.
26. Siddiqi N, Neil C, Bruce M, MacLennan G, Cotton S, Papadopoulou S, Feelisch M, Bunce N, Lim PO, Hildick-Smith D, Horowitz J, Madhani M, Boon N, Dawson D, Kaski JC, Frenneaux M; NIAMI investigators. Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI). Eur Heart J. 2014;35:1255-1262. doi: 10.1093/eurheartj/ehu096.
27. Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P, Cuvier V, Danchin N, Dubois-Randé JL, Engblom H, Erlinge D, Firat H, Halvorsen S, Hansen HS, Hauke W, Heiberg E, Koul S, Larsen AI, Le Corvoisier P, Nordrehaug JE, Paganelli F, Pruss RM, Rousseau H, Schaller S, Sonou G, Tuseth V, Veys J, Vicaut E, Jensen SE. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur Heart J. 2015;36:112-119. doi: 10.1093/eurheartj/ehu331.
28. Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guérin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Randé JL, Unterseeh T, Le Breton H, Béard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M. Cyclosporine before PCI in Patients with Acute Myocardial Infarction. N Engl J Med. 2015;373:1021-1031. doi: 10.1056/ NEJMoa1505489.
29. Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 2004;62:74-85. doi: 10.1016/j.cardiores. 2004.01.006.
30. Yang XM, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol. 2004;44:1103-1110. doi: 10.1016/j.jacc.2004.05.060.
31. Malliaras K, Zhang Y, Seinfeld J, Galang G, Tseliou E, Cheng K, Sun B, Aminzadeh M, Marbán E. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med. 2013;5:191-209. doi: 10.1002/emmm.201201737.
32. Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature. 2008;451:937-942. doi: 10.1038/nature06800.
33. Bolli R, Tang XL, Sanganalmath SK, Rimoldi O, Mosna F, Abdel-Latif A, Jneid H, Rota M, Leri A, Kajstura J. Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation. 2013;128:122-131. doi: 10.1161/ CIRCULATIONAHA.112.001075.
34. Johnston PV, Sasano T, Mills K, Evers R, Lee ST, Smith RR, Lardo AC, Lai S, Steenbergen C, Gerstenblith G, Lange R, Marbán E. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation. 2009;120:1075-83, 7 p following 1083. doi: 10.1161/CIRCULATIONAHA.108.816058.
35. Lee ST, White AJ, Matsushita S, Malliaras K, Steenbergen C, Zhang Y, Li TS, Terrovitis J, Yee K, Simsir S, Makkar R, Marbán E. 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. 2011;57:455-465. doi: 10.1016/j.jacc.2010.07.049.
36. Malliaras K, Smith RR, Kanazawa H, Yee K, Seinfeld J, Tseliou E, Dawkins JF, Kreke M, Cheng K, Luthringer D, Ho CS, Blusztajn A, Valle I, Chowdhury S, Makkar RR, Dharmakumar R, Li D, Marbán L, Marbán E. Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction. Circulation. 2013;128:2764-2775. doi: 10.1161/CIRCULATIONAHA. 113.002863.
37. Kreke M, Smith RR, Marbán L, Marbán E. Cardiospheres and cardiospherederived cells as therapeutic agents following myocardial infarction. Expert Rev Cardiovasc Ther. 2012;10:1185-1194. doi: 10.1586/erc.12.102.
38. Jennings RB, Murry CE, Steenbergen C Jr, Reimer KA. Development of cell injury in sustained acute ischemia. Circulation. 1990;82(3 suppl): II2-I12.
39. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest. 1985;76:1713-1719. doi: 10.1172/JCI112160.
40. Hochman JS, Choo H. Limitation of myocardial infarct expansion by reperfusion independent of myocardial salvage. Circulation. 1987;75:299-306.
41. Freyman T, Polin G, Osman H, Crary J, Lu M, Cheng L, Palasis M, Wilensky RL. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J. 2006;27:1114-1122. doi: 10.1093/eurheartj/ehi818.
42. Perin EC, Silva GV, Assad JA, Vela D, Buja LM, Sousa AL, Litovsky S, Lin J, Vaughn WK, Coulter S, Fernandes MR, Willerson JT. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol. 2008;44:486-495. doi: 10.1016/j.yjmcc.2007.09.012.
43. Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet. 2004;363:783-784. doi: 10.1016/S0140-6736(04)15695-X.
44. Houtgraaf JH, de Jong R, Kazemi K, de Groot D, van der Spoel TI, Arslan F, Hoefer I, Pasterkamp G, Itescu S, Zijlstra F, Geleijnse ML, Serruys PW, Duckers HJ. Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res. 2013;113:153-166. doi: 10.1161/CIRCRESAHA. 112.300730.
45. Lim SY, Kim YS, Ahn Y, Jeong MH, Hong MH, Joo SY, Nam KI, Cho JG, Kang PM, Park JC. The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovasc Res. 2006;70:530-542. doi: 10.1016/j.cardiores.2006.02.016.
46. Malliaras K, Ibrahim A, Tseliou E, Liu W, Sun B, Middleton RC, Seinfeld J, Wang L, Sharifi BG, Marbán E. Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction. EMBO Mol Med. 2014;6:760-777. doi: 10.1002/emmm.201303626.
47. Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, Yamagishi M, Mori H, Kangawa K, Kitamura S. Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol. 2004;287:H2670-H2676. doi: 10.1152/ajpheart. 01071.2003.
48. Henning RJ, Abu-Ali H, Balis JU, Morgan MB, Willing AE, Sanberg PR. Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction. Cell Transplant. 2004;13:729-739.
49. Li TS, Hayashi M, Ito H, Furutani A, Murata T, Matsuzaki M, Hamano K. Regeneration of infarcted myocardium by intramyocardial implantation of ex vivo transforming growth factor-beta-preprogrammed bone marrow stem cells. Circulation. 2005;111:2438-2445. doi: 10.1161/01. CIR.0000167553.49133.81.
50. Boyle AJ, Schuster M, Witkowski P, Xiang G, Seki T, Way K, Itescu S. Additive effects of endothelial progenitor cells combined with ACE inhibition and beta-blockade on left ventricular function following acute myocardial infarction. J Renin Angiotensin Aldosterone Syst. 2005;6:33-37. doi: 10.3317/jraas.2005.004.
51. Yamada Y, Wang XD, Yokoyama S, Fukuda N, Takakura N. Cardiac progenitor cells in brown adipose tissue repaired damaged myocardium. Biochem Biophys Res Commun. 2006;342:662-670. doi: 10.1016/j. bbrc.2006.01.181.
52. Grøgaard HK, Sigurjonsson OE, Brekke M, Kløw NE, Landsverk KS, Lyberg T, Eriksen M, Egeland T, Ilebekk A. Cardiac accumulation of bone marrow mononuclear progenitor cells after intracoronary or intravenous injection in pigs subjected to acute myocardial infarction with subsequent reperfusion. Cardiovasc Revasc Med. 2007;8:21-27. doi: 10.1016/j.carrev. 2006.09.001.
53. Van't Hof W, Mal N, Huang Y, Zhang M, Popovic Z, Forudi F, Deans R, Penn MS. Direct delivery of syngeneic and allogeneic large-scale expanded multipotent adult progenitor cells improves cardiac function after myocardial infarct. Cytotherapy. 2007;9:477-487. doi: 10.1080/14653240701452065.
54. Rajasingh J, Bord E, Hamada H, Lambers E, Qin G, Losordo DW, Kishore R. STAT3-dependent mouse embryonic stem cell differentiation into cardiomyocytes: analysis of molecular signaling and therapeutic efficacy of cardiomyocyte precommitted mES transplantation in a mouse model of myocardial infarction. Circ Res. 2007;101:910-918. doi: 10.1161/CIRCRESAHA. 107.156786.
55. Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J. 2007;28:2667-2677. doi: 10.1093/eurheartj/ehm426.
56. Lu G, Haider HK, Jiang S, Ashraf M. Sca-1+ stem cell survival and engraftment in the infarcted heart: dual role for preconditioning-induced connexin-43. Circulation. 2009;119:2587-2596. doi: 10.1161/CIRCULATIONAHA. 108.827691.
57. Gálvez BG, Covarello D, Tolorenzi R, Brunelli S, Dellavalle A, Crippa S, Mohammed SA, Scialla L, Cuccovillo I, Molla F, Staszewsky L, Maisano F, Sampaolesi M, Latini R, Cossu G. Human cardiac mesoangioblasts isolated from hypertrophic cardiomyopathies are greatly reduced in proliferation and differentiation potency. Cardiovasc Res. 2009;83:707-716. doi: 10.1093/cvr/cvp159.
58. Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A. Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation. 2009;120:408-416. doi: 10.1161/CIRCULATIONAHA.109.865154.
59. Goodchild TT, Robinson KA, Pang W, Tondato F, Cui J, Arrington J, Godwin L, Ungs M, Carlesso N, Weich N, Poznansky MC, Chronos NA. Bone marrow-derived B cells preserve ventricular function after acute myocardial infarction. JACC Cardiovasc Interv. 2009;2:1005-1016. doi: 10.1016/j. jcin.2009.08.010.
60. Chimenti I, Smith RR, Li TS, Gerstenblith G, Messina E, Giacomello A, Marbán E. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010;106:971-980. doi: 10.1161/CIRCRESAHA.109.210682.
61. Shibuya M, Miura T, Fukagawa Y, Akashi S, Oda T, Kawamura S, Ikeda Y, Matsuzaki M. Tongue muscle-derived stem cells express connexin 43 and improve cardiac remodeling and survival after myocardial infarction in mice. Circ J. 2010;74:1219-1226.
62. Bollini S, Cheung KK, Riegler J, Dong X, Smart N, Ghionzoli M, Loukogeorgakis SP, Maghsoudlou P, Dubé KN, Riley PR, Lythgoe MF, De Coppi P. Amniotic fluid stem cells are cardioprotective following acute myocardial infarction. Stem Cells Dev. 2011;20:1985-1994. doi: 10.1089/ scd.2010.0424.
63. Gunetti M, Noghero A, Molla F, Staszewsky LI, de Angelis N, Soldo A, Russo I, Errichiello E, Frasson C, Rustichelli D, Ferrero I, Gualandris A, Berger M, Geuna M, Scacciatella P, Basso G, Marra S, Bussolino F, Latini R, Fagioli F. Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies. Cytotherapy. 2011;13:1140-1152. doi: 10.3109/14653249.2011.597559.
64. Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Giacomello A, Abraham MR, Marbán E. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115:896-908. doi: 10.1161/CIRCULATIONAHA. 106.655209.
65. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marbán L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marbán E. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379:895-904. doi: 10.1016/S0140-6736(12)60195-0.
66. Malliaras K, Makkar RR, Smith RR, Cheng K, Wu E, Bonow RO, Marbán L, Mendizabal A, Cingolani E, Johnston PV, Gerstenblith G, Schuleri KH, Lardo AC, Marbán E. 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. 2014;63:110-122. doi: 10.1016/j.jacc.2013.08.724.
67. Cheng K, Malliaras K, Li TS, Sun B, Houde C, Galang G, Smith J, Matsushita N, Marbán E. Magnetic enhancement of cell retention, engraftment, and functional benefit after intracoronary delivery of cardiac-derived stem cells in a rat model of ischemia/reperfusion. Cell Transplant. 2012;21:1121-1135. doi: 10.3727/096368911X627381.
68. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 2008;103:1204-1219. doi: 10.1161/ CIRCRESAHA.108.176826.
69. Li TS, Cheng K, Lee ST, Matsushita S, Davis D, Malliaras K, Zhang Y, Matsushita N, Smith RR, Marbán E. Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair. Stem Cells. 2010;28:2088-2098. doi: 10.1002/stem.532.
70. Tseliou E, de Couto G, Terrovitis J, Sun B, Weixin L, Marbán L, Marbán E. Angiogenesis, cardiomyocyte proliferation and anti-fibrotic effects underlie structural preservation post-infarction by intramyocardially-injected cardiospheres. PLoS One. 2014;9:e88590. doi: 10.1371/journal.pone.0088590.
71. Tseliou E, Pollan S, Malliaras K, Terrovitis J, Sun B, Galang G, Marbán L, Luthringer D, Marbán E. Allogeneic cardiospheres safely boost cardiac function and attenuate adverse remodeling after myocardial infarction in immunologically mismatched rat strains. J Am Coll Cardiol. 2013;61:1108-1119. doi: 10.1016/j.jacc.2012.10.052.
72. Cho HJ, Lee N, Lee JY, Choi YJ, Ii M, Wecker A, Jeong JO, Curry C, Qin G, Yoon YS. Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart. J Exp Med. 2007;204:3257-3269. doi: 10.1084/jem.20070166.
73. Perez-Ilzarbe M, Agbulut O, Pelacho B, Ciorba C, San Jose-Eneriz E, Desnos M, Hagège AA, Aranda P, Andreu EJ, Menasché P, Prósper F. Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium. Eur J Heart Fail. 2008;10:1065-1072. doi: 10.1016/j.ejheart.2008.08.002.
74. Ibrahim AG, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014;2:606-619. doi: 10.1016/j.stemcr.2014.04.006.
75. Frangogiannis NG. Regulation of the inflammatory response in cardiac repair. Circ Res. 2012;110:159-173. doi: 10.1161/CIRCRESAHA. 111.243162.
76. Frangogiannis NG. The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol. 2014;11:255-265. doi: 10.1038/nrcardio. 2014.28.
77. Nian M, Lee P, Khaper N, Liu P. Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 2004;94:1543-1553. doi: 10.1161/01. RES.0000130526.20854.fa.
78. Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53:31-47.
79. Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365:475-481. doi: 10.1016/S0140-6736(05)17864-7.
80. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011;8:e1001098. doi: 10.1371/journal. pmed.1001098.
81. Patrono C, Baigent C. Nonsteroidal anti-inflammatory drugs and the heart. Circulation. 2014;129:907-916. doi: 10.1161/CIRCULATIONAHA. 113.004480.
82. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.
83. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11:723-737. doi: 10.1038/ nri3073.
84. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958-969. doi: 10.1038/nri2448.
85. Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B, Brija T, Gautier EL, Ivanov S, Satpathy AT, Schilling JD, Schwendener R, Sergin I, Razani B, Forsberg EC, Yokoyama WM, Unanue ER, Colonna M, Randolph GJ, Mann DL. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity. 2014;40:91-104. doi: 10.1016/j. immuni.2013.11.019.
86. Ben-Mordechai T, Holbova R, Landa-Rouben N, Harel-Adar T, Feinberg MS, Abd Elrahman I, Blum G, Epstein FH, Silman Z, Cohen S, Leor J. Macrophage subpopulations are essential for infarct repair with and without stem cell therapy. J Am Coll Cardiol. 2013;62:1890-1901. doi: 10.1016/j. jacc.2013.07.057.
87. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN. Macrophages are required for neonatal heart regeneration. J Clin Invest. 2014;124:1382-1392. doi: 10.1172/JCI72181.
88. Kanazawa H, Tseliou E, Malliaras K, Yee K, Dawkins JF, De Couto G, Smith RR, Kreke M, Seinfeld J, Middleton RC, Gallet R, Cheng K, Luthringer D, Valle I, Chowdhury S, Fukuda K, Makkar RR, Marbán L, Marbán E. 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. 2015;8:322-332. doi: 10.1161/CIRCHEARTFAILURE. 114.001484.
89. de Couto G, Liu W, Tseliou E, Sun B, Makkar N, Kanazawa H, Arditi M, Marbán E. Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction. J Clin Invest. 2015;125:3147-3162. doi: 10.1172/JCI81321.
90. Kanazawa H, Tseliou E, Dawkins JF, De Couto G, Gallet R, Malliaras K, Yee K, Kreke M, Valle I, Smith RR, Middleton RC, Ho CS, Dharmakumar R, Li D, Makkar RR, Fukuda K, Marban L, Marban E. Durable benefits of cellular postconditioning: long-term effects of allogeneic cardiosphere-derived cells infused after reperfusion in pigs with acute myocardial infarction. J Am Heart Assoc. 2016;5:e002796. doi: 10.1161/ JAHA.115.002796.
91. Ibrahim A, Marbán E. Exosomes: fundamental biology and roles in cardiovascular physiology. Annu Rev Physiol. 2016;78:67-83. doi: 10.1146/ annurev-physiol-021115-104929.
92. de Couto G, Makkar N, Marbán E. Cardiosphere-derived cell exosomes confer acute cardioprotection following ischemia-reperfusion injury through macrophage polarization. Circulation. 2015;132(suppl 3):A16991-A16991.
93. Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM, Vera MP, Blackwell TS, Baron RM, Feinberg MW; MICU Registry. MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J Clin Invest. 2012;122:1973-1990. doi: 10.1172/JCI61495.
94. Greenlee-Wacker MC. Clearance of apoptotic neutrophils and resolution of inflammation. Immunol Rev. 2016;273:357-370. doi: 10.1111/ imr.12453.
95. de Couto G, Jaghatspanyan E, Kravets E, Marbán E. Cardiosphere-derived cell exosomes reduce proinflammatory gene expression and enhance efferocytosis of macrophages to reduce infarct size following ischemiareperfusion injury. Circulation. 2016;134(suppl 1):A16656-A16656.
96. Gallet R, Dawkins J, Valle J, Simsolo E, de Couto G, Middleton R, Tseliou E, Luthringer D, Kreke M, Smith RR, Marban L, Ghaleh B, Marban E. 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;38:201-211.
97. Gorenek B. Tachyarrhythmias in percutaneous coronary interventions. J Electrocardiol. 2006;39:412.e1-412.e5. doi: 10.1016/j.jelectrocard. 2006.03.008.
98. Kloner RA. Current state of clinical translation of cardioprotective agents for acute myocardial infarction. Circ Res. 2013;113:451-463. doi: 10.1161/CIRCRESAHA.112.300627.
99. Aminzadeh MA, Tseliou E, Sun B, Cheng K, Malliaras K, Makkar RR, Marbán E. Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy. Eur Heart J. 2015;36:751-762. doi: 10.1093/eurheartj/ehu196.
100. Lauden L, Boukouaci W, Borlado LR, López IP, Sepúlveda P, Tamouza R, Charron D, Al-Daccak R. Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand 1. Circ Res. 2013;112:451-464. doi: 10.1161/CIRCRESAHA.112.276501.
101. Chakravarty T, Makkar RR, Ascheim DD, Traverse JH, Schatz R, DeMaria A, Francis GS, Povsic TJ, Smith RR, Lima JA, Pogoda JM, Marbán L, Henry TD. ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: rationale and design. Cell Transplant. 2017;26:205-214. doi: 10.3727/096368916X692933.
102. Tseliou E, Kanazawa H, Dawkins J, Gallet R, Kreke M, Smith R, Middleton R, Valle J, Marbán L, Kar S, Makkar R, Marbán E. Widespread myocardial delivery of heart-derived stem cells by nonocclusive triple-vessel intracoronary infusion in porcine ischemic cardiomyopathy: superior attenuation of adverse remodeling documented by magnetic resonance imaging and histology. PLoS One. 2016;11:e0144523. doi: 10.1371/journal. pone.0144523.