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Circulation 2005; 111: 11-20.","DOI":"10.1161\/01.CIR.0000151313.18547.A2"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Ling-Ling E, Zhao YS, Guo XM, <i>et al<\/i>. Enrichment of cardiomyocytes derived from mouse embryonic stem cells. J Heart Lung Transplant 2006; 25: 664-74.","DOI":"10.1016\/j.healun.2005.12.007"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Lee RJ, Sievers RE, Gallinghouse GJ, Ursell PC. Development of a model of complete heart block in rats. J Appl Physiol (1985) 1998; 85: 758-63.","DOI":"10.1152\/jappl.1998.85.2.758"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Hattori F, Chen H, Yamashita H, <i>et al<\/i>. Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 2010; 7: 61-6.","DOI":"10.1038\/nmeth.1403"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Morikawa K, Bahrudin U, Miake J, <i>et al<\/i>. 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Br J Pharmacol 1994; 112: 37-42.","DOI":"10.1111\/j.1476-5381.1994.tb13025.x"},{"key":"30","doi-asserted-by":"publisher","unstructured":"30. Swedberg K, Komajda M, B\u00f6hm M, <i>et al<\/i>. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. The Lancet 2010; 376: 875-85.","DOI":"10.1016\/S0140-6736(10)61198-1"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Hashimoto A, Naito AT, Lee JK, <i>et al<\/i>. Generation of induced pluripotent stem cells from patients with duchenne muscular dystrophy and their induction to cardiomyocytes. Int Heart J 2016; 57: 112-7.","DOI":"10.1536\/ihj.15-376"},{"key":"32","doi-asserted-by":"publisher","unstructured":"32. Araki R, Uda M, Hoki Y, <i>et al<\/i>. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 2013; 494: 100-4.","DOI":"10.1038\/nature11807"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. 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