Stem cells are not proarrhythmic: Letting the genie out of the bottle

Circulation

Volumn 119, Issue 13, 2009, Pages 1824-1831

  Ly, Hung Q ^a   Nattel, Stanley ^a,b  

^a MONTREAL HEART INSTITUTE   (Canada)

^b NONE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMIODARONE;

CLINICAL TRIAL; CORONARY ARTERY BYPASS GRAFT; ELECTROPHYSIOLOGY; HEART INFARCTION; HEART PERFORMANCE; HEART PROARRHYTHMIA; HEART VENTRICLE TACHYCARDIA; HEMATOPOIETIC STEM CELL; HUMAN; ISCHEMIC HEART DISEASE; MYOBLAST; PRIORITY JOURNAL; REVIEW; STEM CELL TRANSPLANTATION; ANIMAL; HEART ARRHYTHMIA; METHODOLOGY; NOTE;

ANIMALS; ARRHYTHMIAS, CARDIAC; HUMANS; MYOCARDIAL INFARCTION; STEM CELL TRANSPLANTATION;

EID: 65349147149     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.108.812701     Document Type: Review

References (87)

1. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Stein- berger J, Thom T, Wilson M, Hong Y. Heart disease and stroke statis- tics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117: e25-e146.
2. National Heart, Lung, and Blood Institute. Mortality and Morbidity: 2004 Chartbook on Cardiovascular Lung and Blood Diseases. Bethesda, MD: National Heart, Lung, and Blood Institute; 2004.
3. Yacoub M, Suzuki K, Rosenthal N. The future of regenerative therapy in patients with chronic heart failure. Nat Clin Pract Cardiovasc Med. 2006;3(Suppl 1):S133-S135.
4. Landmesser U, Drexler H. Chronic heart failure: an overview of conventional treatment versus novel approaches. Nat Clin Pract Cardiovasc Med. 2005;2:628-638.
5. Boyle AJ, Schulman SP, Hare JM, Oettgen P. Stem cell therapy for cardiac repair: ready for the next step. Circulation. 2006;114:339-352.
6. Oettgen P, Boyle AJ, Schulman SP, Hare JM. Cardiac stem cell therapy: need for optimization of efficacy and safety monitoring. Circulation. 2006;114:353-358.
7. Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest. 2005;115:572-583.
8. Rosen MR. Are stem cells drugs? The regulation of stem cell research and development. Circulation. 2006;114:1992-2000.
9. Sussman MA, Murry CE. Bones of contention: marrow-derived cells in myocardial regeneration. J Mol Cell Cardiol. 2008;44:950-953.
10. Welt FG, Losordo DW. Cell therapy for acute myocardial infarction: curb your enthusiasm? Circulation. 2006;113:1272-1274.
11. Ben-Dor I, Fuchs S, Kornowski R. Potential hazards and technical considerations associated with myocardial cell transplantation protocols for ischemic myocardial syndrome. J Am Coll Cardiol. 2006;48:1519-1526.
12. Dudley SC Jr. Beware of cells bearing gifts: cell replacement therapy and arrhythmic risk. Circ Res. 2005;97:99-101.
13. Makkar RR, Lill M, Chen PS. Stem cell therapy for myocardial repair: is it arrhythmogenic? J Am Coll Cardiol. 2003;42:2070-2072.
14. Peters NS. Arrhythmias after cell transplantation for myocardial regeneration: natural history or result of the intervention? J Car- diovasc Electrophysiol. 2005;16:1255-1257.
15. Smith RR, Barile L, Messina E, Marban E. Stem cells in the heart: what's the buzz all about? Part 2: arrhythmic risks and clinical studies. Heart Rhythm. 2008;5:880-887.
16. Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin JT, Marolleau JP. Myoblast transplantation for heart failure. Lancet. 2001;357:279-280.
17. Menasche P, Hagege AA, Vilquin JT, Desnos M, Abergel E, Pouzet B, Bel A, Sarateanu S, Scorsin M, Schwartz K, Bruneval P, Benbunan M, Marolleau JP, Duboc D. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003;41:1078-1083.
18. Murry CE, Wiseman RW, Schwartz SM, Hauschka SD. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest. 1996;98:2512-2523.
19. Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, Glower DD, Kraus WE. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998;4:929 -933.
20. Pagani FD, DerSimonian H, Zawadzka A, Wetzel K, Edge AS, Jacoby DB, Dinsmore JH, Wright S, Aretz TH, Eisen HJ, Aaronson KD. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans: histological analysis of cell survival and differentiation. J Am Coll Cardiol. 2003;41:879-888.
21. Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzezniczak J, Rozwadowska N, Kurpisz M. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J. 2004;148: 531-537.
22. Dib N, Michler RE, Pagani FD, Wright S, Kereiakes DJ, Lengerich R, Binkley P, Buchele D, Anand I, Swingen C, Di Carli MF, Thomas JD, Jaber WA, Opie SR, Campbell A, McCarthy P, Yeager M, Dilsizian V, Griffith BP, Korn R, Kreuger SK, Ghazoul M, MacLellan WR, Fonarow G, Eisen HJ, Dinsmore J, Diethrich E. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation. 2005;112:1748-1755.
23. Smits PC, van Geuns RJ, Poldermans D, Bountioukos M, Onderwater EE, Lee CH, Maat AP, Serruys PW. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol. 2003;42:2063-2069.
24. Hendrikx M, Hensen K, Clijsters C, Jongen H, Koninckx R, Bijnens E, Ingels M, Jacobs A, Geukens R, Dendale P, Vijgen J, Dilling D, Steels P, Mees U, Rummens JL. Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial. Circulation.2006;114(Suppl):I-101- I-107.
25. Solomon SD, Zelenkofske S, McMurray JJ, Finn PV, Velazquez E, Ertl G, Harsanyi A, Rouleau JL, Maggioni A, Kober L, White H, Van de Werf F, Pieper K, Califf RM, Pfeffer MA. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med. 2005;352:2581-2588.
26. Hagege AA, Carrion C, Menasche P, Vilquin JT, Duboc D, Marolleau JP, Desnos M, Bruneval P. Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Lancet. 2003;361: 491-492.
27. Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci U S A. 2003;100:7808-7811.
28. Reinecke H, Poppa V, Murry CE. Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. J Mol Cell Cardiol. 2002;34:241-249.
29. Al Attar N, Carrion C, Ghostine S, Garcin I, Vilquin JT, Hagege AA, Menasche P. Long-term (1 year) functional and histological results of autologous skeletal muscle cells transplantation in rat. Cardiovasc Res. 2003;58:142-148.
30. Reinecke H, MacDonald GH, Hauschka SD, Murry CE. Electromechanical coupling between skeletal and cardiac muscle: implications for infarct repair. J Cell Biol. 2000;149:731-740.
31. Abraham MR, Henrikson CA, Tung L, Chang MG, Aon M, Xue T, Li RA, B OR, Marban E. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ Res. 2005;97:159-167.
32. Chang MG, Tung L, Sekar RB, Chang CY, Cysyk J, Dong P, Marban E, Abraham MR. Proarrhythmic potential of mesenchymal stem cell transplantation revealed in an in vitro coculture model. Circulation. 2006;113:1832-1841.
33. Pak HN, Qayyum M, Kim DT, Hamabe A, Miyauchi Y, Lill MC, Frantzen M, Takizawa K, Chen LS, Fishbein MC, Sharifi BG, Chen PS, Makkar R. Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myo- cardial infarction. J Cardiovasc Electrophysiol. 2003;14:841-848.
34. Lai AC, Wallner K, Cao JM, Chen LS, Karagueuzian HS, Fishbein MC, Chen PS, Sharifi BG. Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death. J Cardiovasc Electrophysiol. 2000;11:1345-1351.
35. Yamamoto K, Dang QN, Kennedy SP, Osathanondh R, Kelly RA, Lee RT. Induction of tenascin-C in cardiac myocytes by mechanical deformation: role of reactive oxygen species. J Biol Chem. 1999;274: 21840-21846.
36. Cowan KN, Jones PL, Rabinovitch M. Regression of hypertrophied rat pulmonary arteries in organ culture is associated with suppression of proteolytic activity, inhibition of tenascin-C, and smooth muscle cell apoptosis. Circ Res. 1999;84:1223-1233.
37. Cao JM, Chen LS, KenKnight BH, Ohara T, Lee MH, Tsai J, Lai WW, Karagueuzian HS, Wolf PL, Fishbein MC, Chen PS. Nerve sprouting and sudden cardiac death. Circ Res. 2000;86:816-821.
38. Zhang YM, Hartzell C, Narlow M, Dudley SC Jr. Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. Circulation. 2002;106:1294 -1299.
39. Weiss JN, Chen PS, Qu Z, Karagueuzian HS, Garfinkel A. Ventricular fibrillation: how do we stop the waves from breaking? Circ Res. 2000; 87:1103-1107.
40. Steinberg JS, Gaur A, Sciacca R, Tan E. New-onset sustained ventricular tachycardia after cardiac surgery. Circulation. 1999;99:903-908.
41. Herreros J, Prosper F, Perez A, Gavira JJ, Garcia-Velloso MJ, Barba J, Sanchez PL, Canizo C, Rabago G, Marti-Climent JM, Hernandez M, Lopez-Holgado N, Gonzalez-Santos JM, Martin-Luengo C, Alegria E. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J. 2003;24:2012-2020.
42. Gavira JJ, Herreros J, Perez A, Garcia-Velloso MJ, Barba J, Martin- Herrero F, Canizo C, Martin-Arnau A, Marti-Climent JM, Hernandez M, Lopez-Holgado N, Gonzalez-Santos JM, Martin-Luengo C, Alegria E, Prosper F. Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up. J Thorac CardiovascSurg. 2006;131:799 -804.
43. Siminiak T, Fiszer D, Jerzykowska O, Grygielska B, Rozwadowska N, Kalmucki P, Kurpisz M. Percutaneous trans-coronary-venous transplantation of autologous skeletal myoblasts in the treatment of post-infarction myocardial contractility impairment: the POZNAN trial. Eur Heart J. 2005;26:1188 -1195.
44. Chachques JC, Herreros J, Trainini J, Juffe A, Rendal E, Prosper F, Genovese J. Autologous human serum for cell culture avoids the implanation of cardioverter-defibrillators in cellular cardiomyoplasty. Int J Cardiol. 2004;95 (Suppl 1):S29 -S33.
45. Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, Vilquin JT, Marolleau JP, Seymour B, Larghero J, Lake S, Chatellier G, Solomon S, Desnos M, Hagege AA. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation.Circulation. 2008;117:1189-1200.
46. Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J, Vanderheyden M, Kim HS, Kang HJ, Strauer BE, Vetrovec GW. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol. 2007;50:1761-1767.
47. Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow- derived cells for cardiac repair: a systematic review and meta-analysis.Arch Intern Med. 2007;167:989-997.
48. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Hols- chermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355:1210-1221.
49. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S. Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J. 2007;28:766-772.
50. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation. 2006;113:1287-1294.
51. Beeres SL, Bax JJ, Dibbets-Schneider P, Stokkel MP, Fibbe WE, van der Wall EE, Schalij MJ, Atsma DE. Sustained effect of autologous bone marrow mononuclear cell injection in patients with refractory angina pectoris and chronic myocardial ischemia: twelve-month follow-up results. Am Heart J. 2006;152:684.e611-e686.
52. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV, Mesquita CT, Belem L, Vaughn WK, Rangel FO, Assad JA, Carvalho AC, Branco RV, Rossi MI, Dohmann HJ, Willerson JT. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation. 2004;110(Suppl):II-213- II-218.
53. Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet. 2003;361:47-49.
54. Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, Baffour R, Waksman R, Weissman NJ, Cerqueira M, Leon MB, Epstein SE. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol. 2003;41:1721-1724.
55. Strauer BE, Brehm M, Zeus T, Bartsch T, Schannwell C, Antke C, Sorg RV, Kogler G, Wernet P, Muller HW, Kostering M. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study.J Am Coll Cardiol. 2005;46:1651-1658.
56. Mocini D, Staibano M, Mele L, Giannantoni P, Menichella G, Colivicchi F, Sordini P, Salera P, Tubaro M, Santini M. Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting. Am Heart J. 2006;151:192-197.
57. Beeres SL, Zeppenfeld K, Bax JJ, Dibbets-Schneider P, Stokkel MP,Fibbe WE, van der Wall EE, Atsma DE, Schalij MJ. Electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic ischemic heart disease. Heart Rhythm. 2007;4: 257-265.
58. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, Kalantzi M, Herbots L, Sinnaeve P, Dens J, Maertens J, Rademakers F, Dymarkowski S, Gheysens O, Van Cleemput J, Bormans G, Nuyts J, Belmans A, Mortelmans L, Boogaerts M, Van de Werf F. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet. 2006;367:113-121.
59. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006;355:1222-1232.
60. Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, De Bondt P, Van Haute I, Lootens N, Heyndrickx G, Wijns W. Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation. 2005;112(Suppl):I-178-I-183.
61. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Bre- idenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary autologous bone- marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364:141-148.
62. Katritsis DG, Sotiropoulou PA, Karvouni E, Karabinos I, Korovesis S, Perez SA, Voridis EM, Papamichail M. Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv. 2005;65:321-329.
63. Fernandes S, Amirault JC, Lande G, Nguyen JM, Forest V, Bignolais O, Lamirault G, Heudes D, Orsonneau JL, Heymann MF, Charpentier F, Lemarchand P. Autologous myoblast transplantation after myo- cardial infarction increases the inducibility of ventricular arrhythmias. Cardiovasc Res. 2006;69:348-358.
64. Mills WR, Mal N, Kiedrowski MJ, Unger R, Forudi F, Popovic ZB, Penn MS, Laurita KR. Stem cell therapy enhances electrical viability in myo-cardial infarction. J Mol Cell Cardiol. 2007;42:304-314.
65. Soliman AM, Krucoff MW, Crater S, Morimoto Y, Taylor DA. Celllocation may be a primary determinant of safety after myoblast transplantation into the infarcted heart. J Am Coll Cardiol. 2004;43(Suppl):A15. Abstract.
66. Fouts K, Fernandes B, Mal N, Liu J, Laurita KR. Electrophysiological consequence of skeletal myoblast transplantation in normal and infarcted canine myocardium. Heart Rhythm. 2006;3:452-461.
67. Fukushima S, Varela-Carver A, Coppen SR, Yamahara K, Felkin LE, Lee J, Barton PJ, Terracciano CM, Yacoub MH, Suzuki K. Direct intramyo- cardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model.Circulation. 2007;115:2254-2261.
68. Zebedin E, Mille M, Speiser M, Zarrabi T, Sandtner W, Latzenhofer B, Todt H, Hilber K. C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment. Am J Physiol Heart Circ Physiol. 2007;292:H439-H450.
69. Halbach M, Pfannkuche K, Pillekamp F, Ziomka A, Hannes T, Reppel M, Hescheler J, Muller-Ehmsen J. Electrophysiological maturation and integration of murine fetal cardiomyocytes after transplantation. Circ Res. 2007;101:484-492.
70. Ince H, Petzsch M, Rehders TC, Chatterjee T, Nienaber CA. Transcath- eter transplantation of autologous skeletal myoblasts in postinfarction patients with severe left ventricular dysfunction. J Endovasc Ther. 2004;11:695-704.
71. Unzek S, Zhang M, Mal N, Mills WR, Laurita KR, Penn MS. SDF-1 recruits cardiac stem cell-like cells that depolarize in vivo. Cell Transplant. 2007;16:879-886.
72. Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Gia- comello A, Abraham MR, Marban E. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 2007;115:896-908.
73. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861-872.
74. Mauritz C, Schwanke K, Reppel M, Neef S, Katsirntaki K, Maier LS, Nguemo F, Menke S, Haustein M, Hescheler J, Hasenfuss G, Martin U. Generation of functional murine cardiac myocytes from induced pluri- potent stem cells. Circulation. 2008;118:507-517.
75. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11:367-368.
76. Zhang D, Fan GC, Zhou X, Zhao T, Pasha Z, Xu M, Zhu Y, Ashraf M, Wang Y. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol. 2008;44:281-292.
77. Roell W, Lewalter T, Sasse P, Tallini YN, Choi BR, Breitbach M, Doran R, Becher UM, Hwang SM, Bostani T, von Maltzahn J, Hofmann A, Reining S, Eiberger B, Gabris B, Pfeifer A, Welz A, Willecke K, Salama G, Schrickel JW, Kotlikoff MI, Fleischmann BK. Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature. 2007;450:819-824.
78. Rubart M, Soonpaa MH, Nakajima H, Field LJ. Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation. J Clin Invest. 2004;114:775-783.
79. Pedrotty DM, Klinger RY, Badie N, Hinds S, Kardashian A, Bursac N. Structural coupling of cardiomyocytes and noncardiomyocytes: quantitative comparisons using a novel micropatterned cell pair assay.Am J Physiol Heart Circ Physiol. 2008;295:H390-H400.
80. Potapova I, Plotnikov A, Lu Z, Danilo P Jr, Valiunas V, Qu J, Doronin S, Zuckerman J, Shlapakova IN, Gao J, Pan Z, Herron AJ, Robinson RB, Brink PR, Rosen MR, Cohen IS. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res. 2004;94: 952-959.
81. Satin J, Kehat I, Caspi O, Huber I, Arbel G, Itzhaki I, Magyar J, Schroder EA, Perlman I, Gepstein L. Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. J Physiol. 2004; 559(Pt 2):479-496.
82. Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R, Arbel G, Huber I, Satin J, Itskovitz-Eldor J, Gepstein L. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004;22:1282-1289.
83. Duffy HS. Cardiac connections: the antiarrhythmic solution? N Engl J Med. 2008;358:1397-1398.
84. Amit G, Qin H, Donahue JK. Biological therapies for atrial fibrillation. J Cardiovasc Pharmacol. 2008;52:222-227.
85. Sasano T, McDonald AD, Kikuchi K, Donahue JK. Molecular ablation of ventricular tachycardia after myocardial infarction. Nat Med. 2006;12: 1256 -1258.
86. Chang SA, Kim HK, Lee HY, Choi SY, Koo BK, Kim YJ, Sohn DW, Oh BH, Park YB, Choi YS, Kang HJ, Kim HS. Restoration of left ventricular synchronous contraction after acute myocardial infarction by stem cell therapy: new insights into the therapeutic implication of stem cell therapy for acute myocardial infarction. Heart. 2008;94:995-1001.
87. Yu CM, Zhang Q, Fung JW, Chan HC, Chan YS, Yip GW, Kong SL, Lin H, Zhang Y, Sanderson JE. A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging. J Am Coll Cardiol. 2005;45:677-684.