Abstract
While other cell-based therapies for ischemic heart disease are generally understood to operate through indirect, so-called “paracrine” mechanisms of action (e.g., by promoting angiogenesis or attenuating adverse ventricular remodeling), cardiomyocyte transplantation aims to repopulate the infarct scar with functionally integrated new myocardium that will directly contribute to contractile function. Early proof of concept for this “direct remuscularization” strategy came from preclinical studies in rodent models in which neonatal and fetal cardiomyocytes were shown to stably engraft within the infarct scar and mediate beneficial effects. More recently, pluripotent stem cells (PSCs) have drawn considerable attention as a more practical, highly scalable source of cardiomyocytes, and these PSC-derived cardiomyocytes have shown considerable promise in both small- and large-animal models of post-infarct heart failure. In this chapter, we review the status of preclinical studies of cardiomyocyte transplantation, describe the significant remaining barriers to clinical translation, and consider potential target patient populations and study design for a first-in-human study of PSC-derived cardiomyocyte transplantation in ischemic heart disease.
This is a preview of subscription content, log in via an institution to check access.
References
Ahmad R, Wolber W, Eckardt S et al (2012) Functional neuronal cells generated by human parthenogenetic stem cells. PLoS One 7(8):e42800. doi:10.1371/journal.pone.0042800
Amado LC, Saliaris AP, Schuleri KH et al (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 102(32):11474–11479
Atkins BZ, Lewis CW, Kraus WE et al (1999a) Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ. Ann Thorac Surg 67(1):124–129
Atkins BZ, Hueman MT, Meuchel JM et al (1999b) Myogenic cell transplantation improves in vivo regional performance in infarcted rabbit myocardium. J Heart Lung Transplant 18(12):1173–1180
Baheiraei N, Yeganeh H, Ai J et al (2015) Preparation of a porous conductive scaffold from aniline pentamer-modified polyurethane/PCL blend for cardiac tissue engineering. J Biomed Mater Res A 103(10):3179–3187. doi:10.1002/jbm.a.35447
Balsam LB, Wagers AJ, Christensen JL et al (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428(6983):668–673. doi:10.1038/nature02460
Behfar A, Perez-Terzic C, Faustino RS et al (2007) Cardiopoietic programming of embryonic stem cells for tumor-free heart repair. J Exp Med 204(2):405–420
Bel A, Planat-Bernard V, Saito A et al (2010) Composite cell sheets: a further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation 122(11 Suppl):S118–S123. doi:10.1161/CIRCULATIONAHA.109.927293
Bellin M, Casini S, Davis RP et al (2013) Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome. EMBO J 32(24):3161–3175. doi:10.1038/emboj.2013.240
Ben-David U, Nudel N, Benvenisty N (2013) Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells. Nat Commun 4:1992. doi:10.1038/ncomms2992
Ben-David U, Arad G, Weissbein U et al (2014) Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells. Nat Commun 5:4825. doi:10.1038/ncomms5825
Bergmann O, Bhardwaj RD, Bernard S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102. doi:10.1126/science.1164680
Bergmann O, Zdunek S, Felker A et al (2015) Dynamics of cell generation and turnover in the human heart. Cell 161(7):1566–1575. doi:10.1016/j.cell.2015.05.026
Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415(6868):198–205. doi:10.1038/415198a
Bett GC, Kaplan AD, Lis A et al (2013) Electronic “expression” of the inward rectifier in cardiocytes derived from human-induced pluripotent stem cells. Heart Rhythm 10(12):1903–1910. doi:10.1016/j.hrthm.2013.09.061
Biktashev VN, Arutunyan A, Sarvazyan NA (2008) Generation and escape of local waves from the boundary of uncoupled cardiac tissue. Biophys J 94(9):3726–3738. doi:10.1529/biophysj.107.117630
Blin G, Nury D, Stefanovic S et al (2010) A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J Clin Invest 120(4):1125–1139. doi:10.1172/JCI40120
Brevini TA, Pennarossa G, Antonini S et al (2009) Cell lines derived from human parthenogenetic embryos can display aberrant centriole distribution and altered expression levels of mitotic spindle check-point transcripts. Stem Cell Rev 5(4):340–352. doi:10.1007/s12015-009-9086-9
Burridge PW, Matsa E, Shukla P et al (2014) Chemically defined generation of human cardiomyocytes. Nat Methods 11(8):855–860. doi:10.1038/nmeth.2999
Cai J, Yi FF, Yang XC et al (2007) Transplantation of embryonic stem cell-derived cardiomyocytes improves cardiac function in infarcted rat hearts. Cytotherapy 9(3):283–291
Carvalho JL, de Carvalho PH, Gomes DA et al (2012) Characterization of decellularized heart matrices as biomaterials for regular and whole organ tissue engineering and initial recellularization with ips cells. J Tissue Sci Eng Suppl 11:002. doi:10.4172/2157-7552.S11-002
Caspi O, Huber I, Kehat I et al (2007a) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50(19):1884–1893
Caspi O, Lesman A, Basevitch Y et al (2007b) Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ Res 100(2):263–272
Caspi O, Itzhaki I, Kehat I et al (2009) In vitro electrophysiological drug testing using human embryonic stem cell derived cardiomyocytes. Stem Cells Dev 18(1):161–172. doi:10.1089/scd.2007.0280
Caulfield JB, Leinbach R, Gold H (1976) The relationship of myocardial infarct size and prognosis. Circulation 53(3 Suppl):I141–I144
Chan HY, Keung W, Li RA et al (2015) Morphometric analysis of human embryonic stem cell-derived ventricular cardiomyocytes: determining the maturation state of a population by quantifying parameters in individual cells. Stem Cells Int 2015:586908. doi:10.1155/2015/586908
Chen VC, Couture LA (2015) The suspension culture of undifferentiated human pluripotent stem cells using spinner flasks. Methods Mol Biol 1283:13–21. doi:10.1007/7651_2014_118
Chen QZ, Ishii H, Thouas GA et al (2010) An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart. Biomaterials 31(14):3885–3893. doi:10.1016/j.biomaterials.2010.01.108
Chen JX, Krane M, Deutsch MA et al (2012) Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5. Circ Res 111(1):50-55. doi:10.1161/CIRCRESAHA.112.270264
Chen Y, Wang J, Shen B et al (2015) Engineering a freestanding biomimetic cardiac patch using biodegradable poly(lactic-co-glycolic acid) (PLGA) and human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs). Macromol Biosci 15(3):426–436. doi:10.1002/mabi.201400448
Chong JJ, Murry CE (2014) Cardiac regeneration using pluripotent stem cells--progression to large animal models. Stem Cell Res 13(3 Pt B):654–665. doi:10.1016/j.scr.2014.06.005
Chong JJ, Yang X, Don CW et al (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510(7504):273–277. doi:10.1038/nature13233
Cibelli JB, Cunniff K, Vrana KE (2006) Embryonic stem cells from parthenotes. Methods Enzymol 418:117–135
Citro L, Naidu S, Hassan F et al (2014) Comparison of human induced pluripotent stem-cell derived cardiomyocytes with human mesenchymal stem cells following acute myocardial infarction. PLoS One 9(12):e116281. doi:10.1371/journal.pone.0116281
Condic ML, Rao M (2008) Regulatory issues for personalized pluripotent cells. Stem Cells 26(11):2753–2758. doi:10.1634/stemcells.2008-0421
Cordeiro JM, Nesterenko VV, Sicouri S et al (2013) Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes. J Mol Cell Cardiol 60:36–46. doi:10.1016/j.yjmcc.2013.03.014
Dai W, Field LJ, Rubart M et al (2007) Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts. J Mol Cell Cardiol 43(4):504–516
Daughtry B, Mitalipov S (2014) Concise review: parthenote stem cells for regenerative medicine: genetic, epigenetic, and developmental features. Stem Cells Transl Med 3(3):290–298. doi:10.5966/sctm.2013-0127
Deuse T, Seifert M, Tyan D et al (2011) Immunobiology of naive and genetically modified HLA-class-I-knockdown human embryonic stem cells. J Cell Sci 124(Pt 17):3029–3037. doi:10.1242/jcs.087718
Didie M, Christalla P, Rubart M et al (2013) Parthenogenetic stem cells for tissue-engineered heart repair. J Clin Invest 123(3):1285–1298. doi:10.1172/JCI66854
Doi D, Morizane A, Kikuchi T et al (2012a) Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson's disease. Stem Cells 30(5):935–945. doi:10.1002/stem.1060
Doi D, Morizane A, Kikuchi T et al (2012b) Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson's disease. Stem Cells 30(5):935–945. doi:10.1002/stem.1060
Drawnel FM, Boccardo S, Prummer M et al (2014) Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells. Cell Rep 9(3):810–821. doi:10.1016/j.celrep.2014.09.055
Drouin E, Lande G, Charpentier F (1998) Amiodarone reduces transmural heterogeneity of repolarization in the human heart. J Am Coll Cardiol 32(4):1063–1067
Dubois NC, Craft AM, Sharma P et al (2011) SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat Biotechnol 29(11):1011–1018. doi:10.1038/nbt.2005
Etzion S, Battler A, Barbash IM et al (2001) Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol Cell Cardiol 33(7):1321–1330. doi:10.1006/jmcc. 2000.1391
Evans SM, Yelon D, Conlon FL et al (2010) Myocardial lineage development. Circ Res 107(12):1428–1444. doi:10.1161/CIRCRESAHA.110.227405
Fatkhudinov T, Bolshakova G, Arutyunyan I et al (2015) Bone marrow-derived multipotent stromal cells promote myocardial fibrosis and reverse remodeling of the left ventricle. Stem Cells Int 2015:746873. doi:10.1155/2015/746873
Fernandes S, Naumova AV, Zhu WZ et al (2010) Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats. J Mol Cell Cardiol 49(6):941–949. doi:10.1016/j.yjmcc.2010.09.008
Fernandes S, Chong JJ, Paige SL et al (2015) Comparison of human embryonic stem cell-derived cardiomyocytes, cardiovascular progenitors, and bone marrow mononuclear cells for cardiac repair. Stem Cell Reports 5(5):753–762. doi:10.1016/j.stemcr. 2015.09.011
Fico A, De Chevigny A, Egea J et al (2012) Modulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotency. Stem Cells 30(9):1863–1874. doi:10.1002/stem.1165
Fisher DJ (1984) Oxygenation and metabolism in the developing heart. Semin Perinatol 8(3):217–225
Foldes G, Mioulane M, Wright JS et al (2011) Modulation of human embryonic stem cell-derived cardiomyocyte growth: a testbed for studying human cardiac hypertrophy? J Mol Cell Cardiol 50(2):367–376. doi:10.1016/j.yjmcc.2010.10.029
Fu Y, Huang C, Xu X et al (2015) Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails. Cell Res 25(9):1013–1024. doi:10.1038/cr.2015.99
Fujimoto KL, Clause KC, Liu LJ et al (2011) Engineered fetal cardiac graft preserves its cardiomyocyte proliferation within postinfarcted myocardium and sustains cardiac function. Tissue Eng Part A 17(5–6):585–596. doi:10.1089/ten.TEA.2010.0259
Funakoshi S, Miki K, Takaki T et al (2016) Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes. Sci Rep 6:19111. doi:10.1038/srep19111
Furuta A, Miyoshi S, Itabashi Y et al (2006) Pulsatile cardiac tissue grafts using a novel three-dimensional cell sheet manipulation technique functionally integrates with the host heart, in vivo. Circ Res 98(5):705–712
Gadue P, Huber TL, Nostro MC et al (2005) Germ layer induction from embryonic stem cells. Exp Hematol 33(9):955–964. doi:10.1016/j.exphem.2005.06.009
Gandolfi F, Vanelli A, Pennarossa G et al (2011) Large animal models for cardiac stem cell therapies. Theriogenology 75(8):1416–1425. doi:10.1016/j.theriogenology.2011.01.026
Gerdes AM, Onodera T, Tamura T et al (1998) New method to evaluate myocyte remodeling from formalin-fixed biopsy and autopsy material. J Card Fail 4(4):343–348
Guyette JP, Gilpin SE, Charest JM et al (2014) Perfusion decellularization of whole organs. Nat Protoc 9(6):1451–1468. doi:10.1038/nprot.2014.097
Guyette JP, Charest J, Mills RW et al (2016) Bioengineering human myocardium on native extracellular matrix. Circ Res 118(1):56–72. doi:10.1161/CIRCRESAHA.115.306874
Habib M, Shapira-Schweitzer K, Caspi O et al (2011) A combined cell therapy and in-situ tissue-engineering approach for myocardial repair. Biomaterials 32(30):7514–7523. doi:10.1016/j.biomaterials.2011.06.049
Hassink RJ, Pasumarthi KB, Nakajima H et al (2008) Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction. Cardiovasc Res 78(1):18–25
Hattori F, Chen H, Yamashita H et al (2010) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7(1):61–66. doi:10.1038/nmeth.1403
He JQ, Ma Y, Lee Y et al (2003) Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 93(1):32–39. doi:10.1161/01.RES.0000080317.92718.99
Hemmi N, Tohyama S, Nakajima K et al (2014) A massive suspension culture system with metabolic purification for human pluripotent stem cell-derived cardiomyocytes. Stem Cells Transl Med 3(12):1473–1483. doi:10.5966/sctm.2014-0072
Hibino N, Duncan DR, Nalbandian A et al (2012) Evaluation of the use of an induced pluripotent stem cell sheet for the construction of tissue-engineered vascular grafts. J Thorac Cardiovasc Surg 143(3):696–703. doi:10.1016/j.jtcvs.2011.06.046
Hirt MN, Boeddinghaus J, Mitchell A et al (2014) Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J Mol Cell Cardiol 74:151–161. doi:10.1016/j.yjmcc.2014.05.009
Hu S, Huang M, Nguyen PK et al (2011) Novel microRNA prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation. Circulation 124(11 Suppl):S27–S34. doi:10.1161/CIRCULATIONAHA.111.017954
Huber BC, Ransohoff JD, Ransohoff KJ et al (2013) Costimulation-adhesion blockade is superior to cyclosporine a and prednisone immunosuppressive therapy for preventing rejection of differentiated human embryonic stem cells following transplantation. Stem Cells 31(11):2354–2363. doi:10.1002/stem.1501
Ieda M, Fu JD, Delgado-Olguin P et al (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142(3):375–386. doi:10.1016/j.cell.2010.07.002
Isaev DA, Garitaonandia I, Abramihina TV et al (2012) In vitro differentiation of human parthenogenetic stem cells into neural lineages. Regen Med 7(1):37–45. doi:10.2217/rme.11.110
Iso Y, Spees JL, Serrano C et al (2007) Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment. Biochem Biophys Res Commun 354(3):700–706
Itskovitz-Eldor J, Schuldiner M, Karsenti D et al (2000) Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 6(2):88–95
Itzhaki I, Maizels L, Huber I et al (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471(7337):225–229. doi:10.1038/nature09747
Jayawardena TM, Egemnazarov B, Finch EA et al (2012) MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 110(11):1465–1473. doi:10.1161/CIRCRESAHA.112.269035
Johnston PV, Sasano T, Mills K et al (2009) Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation 120(12):1075–1083., 7 p following 1083. doi:10.1161/CIRCULATIONAHA.108.816058
Jonsson MK, Vos MA, Mirams GR et al (2012) Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG. J Mol Cell Cardiol 52(5):998–1008. doi:10.1016/j.yjmcc.2012.02.002
Jopling C, Sleep E, Raya M et al (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464(7288):606–609. doi:10.1038/nature08899
Kadota S, Minami I, Morone N et al (2013) Development of a reentrant arrhythmia model in human pluripotent stem cell-derived cardiac cell sheets. Eur Heart J 34(15):1147–1156. doi:10.1093/eurheartj/ehs418
Kamakura T, Makiyama T, Sasaki K et al (2013) Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture. Circ J 77(5):1307–1314
Karabekian Z, Ding H, Gtybayeva G et al (2015) HLA class I depleted hESC as a source of hypoimmunogenic cells for tissue engineering applications. Tissue Eng Part A. doi:10.1089/ten.TEA.2015.0105
Karakikes I, Senyei GD, Hansen J et al (2014) Small molecule-mediated directed differentiation of human embryonic stem cells toward ventricular cardiomyocytes. Stem Cells Transl Med 3(1):18–31. doi:10.5966/sctm.2013-0110
Katritsis DG, Sotiropoulou PA, Karvouni E et al (2005) Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv 65(3):321–329. doi:10.1002/ccd.20406
Kawamura M, Miyagawa S, Miki K et al (2012) Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126(11 Suppl 1):S29–S37. doi:10.1161/CIRCULATIONAHA.111.084343
Kawasaki T, Kirita Y, Kami D et al (2015) Novel detergent for whole organ tissue engineering. J Biomed Mater Res A 103(10):3364–3373. doi:10.1002/jbm.a.35474
Kehat I, Kenyagin-Karsenti D, Snir M et al (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108(3):407–414. doi:10.1172/JCI12131
Kehat I, Khimovich L, Caspi O et al (2004) Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22(10):1282–1289. doi:10.1038/nbt1014
Kempf H, Olmer R, Kropp C et al (2014) Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cells in scalable suspension culture. Stem Cell Rep 3(6):1132–1146. doi:10.1016/j.stemcr.2014.09.017
Kerscher P, Bussie BS, DeSimone KM et al (2015) Characterization of mitochondrial populations during stem cell differentiation. Methods Mol Biol 1264:453–463. doi:10.1007/978-1-4939-2257-4_37
Khan M, Xu Y, Hua S et al (2015) Evaluation of changes in morphology and function of human induced pluripotent stem cell derived cardiomyocytes (HiPSC-CMs) cultured on an aligned-nanofiber cardiac patch. PLoS One 10(5):e0126338. doi:10.1371/journal.pone.0126338
Kikuchi K, Holdway JE, Werdich AA et al (2010) Primary contribution to zebrafish heart regeneration by gata 4(+) cardiomyocytes. Nature 464(7288):601–605. doi:10.1038/nature08804
Kim C, Majdi M, Xia P et al (2010) Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation. Stem Cells Dev 19(6):783–795. doi:10.1089/scd.2009.0349
Kinder SJ, Tsang TE, Quinlan GA et al (1999) The orderly allocation of mesodermal cells to the extraembryonic structures and the anteroposterior axis during gastrulation of the mouse embryo. Development 126(21):4691–4701
Klug MG, Soonpaa MH, Koh GY et al (1996) Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts. J Clin Invest 98(1):216–224. doi:10.1172/JCI118769
Kobayashi Y, Okada Y, Itakura G et al (2012) Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity. PLoS One 7(12):e52787. doi:10.1371/journal.pone.0052787
Kolossov E, Bostani T, Roell W et al (2006) Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. J Exp Med 203(10):2315–2327. doi:10.1084/jem.20061469
Komae H, Sekine H, Dobashi I et al (2015) Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells. J Tissue Eng Regen Med 11(3):926–935. doi:10.1002/term.1995
Kozubenko N, Turnovcova K, Kapcalova M et al (2010) Analysis of in vitro and in vivo characteristics of human embryonic stem cell-derived neural precursors. Cell Transplant 19(4):471–486. doi:10.3727/096368909X484707
Kreutziger KL, Muskheli V, Johnson P et al (2011) Developing vasculature and stroma in engineered human myocardium. Tissue Eng Part A 17(9–10):1219–1228. doi:10.1089/ten.TEA.2010.0557
Kuppusamy KT, Jones DC, Sperber H et al (2015) Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes. Proc Natl Acad Sci U S A 112(21):E2785–E2794. doi:10.1073/pnas.1424042112
Kutschka I, Chen IY, Kofidis T et al (2006a) Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. Circulation 114(1 Suppl):I167–I173. doi:10.1161/CIRCULATIONAHA.105.001297
Kutschka I, Kofidis T, Chen IY et al (2006b) Adenoviral human BCL-2 transgene expression attenuates early donor cell death after cardiomyoblast transplantation into ischemic rat hearts. Circulation 114(1 Suppl):I174–I180. doi:10.1161/CIRCULATIONAHA.105.001370
van Laake LW, Passier R, Monshouwer-Kloots J et al (2007) Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. Stem Cell Res 1(1):9–24. doi:10.1016/j.scr.2007.06.001
van Laake LW, Passier R, Doevendans PA et al (2008) Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. Circ Res 102(9):1008–1010. doi:10.1161/CIRCRESAHA.108.175505
Laflamme MA, Gold J, Xu C et al (2005) Formation of human myocardium in the rat heart from human embryonic stem cells. Am J Pathol 167(3):663–671. doi:10.1016/S0002-9440(10)62041-X
Laflamme MA, Chen KY, Naumova AV et al (2007a) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25(9):1015–1024. doi:10.1038/nbt1327
Laflamme MA, Zbinden S, Epstein SE et al (2007b) Cell-based therapy for myocardial ischemia and infarction: pathophysiological mechanisms. Annu Rev Pathol 2:307–339. doi:10.1146/annurev.pathol.2.010506.092038
Lam AT, Li J, Chen AK et al (2015) Improved human pluripotent stem cell attachment and spreading on xeno-free laminin-521-coated microcarriers results in efficient growth in agitated cultures. Biores Open Access 4(1):242–257. doi:10.1089/biores.2015.0010
Lecina M, Ting S, Choo A et al (2010) Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures. Tissue Eng Part C Methods 16(6):1609–1619. doi:10.1089/ten.TEC.2010.0104
Lee P, Klos M, Bollensdorff C et al (2012) Simultaneous voltage and calcium mapping of genetically purified human induced pluripotent stem cell-derived cardiac myocyte monolayers. Circ Res 110(12):1556–1563. doi:10.1161/CIRCRESAHA.111.262535
Leiker M, Suzuki G, Iyer VS et al (2008) Assessment of a nuclear affinity labeling method for tracking implanted mesenchymal stem cells. Cell Transplant 17(8):911–922
Leor J, Patterson M, Quinones MJ et al (1996) Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation 94(9 Suppl):II332–II336
Leschik J, Caron L, Yang H et al (2015) A view of bivalent epigenetic marks in two human embryonic stem cell lines reveals a different cardiogenic potential. Stem Cells Dev 24(3):384–392. doi:10.1089/scd. 2014.0345
Lesman A, Habib M, Caspi O et al (2010) Transplantation of a tissue-engineered human vascularized cardiac muscle. Tissue Eng Part A 16(1):115–125. doi:10.1089/ten.TEA.2009.0130
Li RK, Jia ZQ, Weisel RD et al (1996) Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 62(3):654–660. discussion 660-1
Li GR, Feng J, Yue L et al (1998) Transmural heterogeneity of action potentials and Ito1 in myocytes isolated from the human right ventricle. Am J Phys 275(2 Pt 2):H369–H377
Li J, He J, Lin G et al (2014) Inducing human parthenogenetic embryonic stem cells into isletlike clusters. Mol Med Rep 10(6):2882–2890. doi:10.3892/mmr.2014.2588
Lian X, Hsiao C, Wilson G et al (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A 109(27):E1848–E1857. doi:10.1073/pnas.1200250109
Lian X, Zhang J, Azarin SM et al (2013) Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/beta-catenin signaling under fully defined conditions. Nat Protoc 8(1):162–175. doi:10.1038/nprot.2012.150
Liau B, Christoforou N, Leong KW et al (2011) Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function. Biomaterials 32(35):9180–9187. doi:10.1016/j.biomaterials.2011.08.050
Lieu DK, Liu J, Siu CW et al (2009) Absence of transverse tubules contributes to non-uniform ca(2+) wavefronts in mouse and human embryonic stem cell-derived cardiomyocytes. Stem Cells Dev 18(10):1493–1500. doi:10.1089/scd.2009.0052
Lin H, Lei J, Wininger D et al (2003) Multilineage potential of homozygous stem cells derived from metaphase II oocytes. Stem Cells 21(2):152–161. doi:10.1634/stemcells.21-2-152
Lin Q, Fu Q, Zhang Y et al (2010) Tumourigenesis in the infarcted rat heart is eliminated through differentiation and enrichment of the transplanted embryonic stem cells. Eur J Heart Fail 12(11):1179–1185. doi:10.1093/eurjhf/hfq144
Liu J, Lieu DK, Siu CW et al (2009) Facilitated maturation of Ca2+ handling properties of human embryonic stem cell-derived cardiomyocytes by calsequestrin expression. Am J Phys Cell Phys 297(1):C152–C159. doi:10.1152/ajpcell.00060.2009
Liu W, Yin Y, Jiang Y et al (2011a) Genetic and epigenetic X-chromosome variations in a parthenogenetic human embryonic stem cell line. J Assist Reprod Genet 28(4):303–313. doi:10.1007/s10815-010-9517-1
Liu J, van Mil A, Vrijsen K et al (2011b) MicroRNA-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting RIP1. J Cell Mol Med 15(7):1474–1482. doi:10.1111/j.1582-4934.2010.01104.x
Liu J, Sun N, Bruce MA et al (2012) Atomic force mechanobiology of pluripotent stem cell-derived cardiomyocytes. PLoS One 7(5):e37559. doi:10.1371/journal.pone.0037559
Lopaschuk GD, Spafford MA, Marsh DR (1991) Glycolysis is predominant source of myocardial ATP production immediately after birth. Am J Phys 261(6 Pt 2):H1698–H1705
Lu P, Chen J, He L et al (2013a) Generating hypoimmunogenic human embryonic stem cells by the disruption of beta 2-microglobulin. Stem Cell Rev 9(6):806–813. doi:10.1007/s12015-013-9457-0
Lu TY, Lin B, Kim J et al (2013b) Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun 4:2307. doi:10.1038/ncomms3307
Lundy SD, Zhu WZ, Regnier M et al (2013) Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cells Dev 22(14):1991–2002. doi:10.1089/scd.2012.0490
Luo J, Weaver MS, Cao B et al (2014a) Cobalt protoporphyrin pretreatment protects human embryonic stem cell-derived cardiomyocytes from hypoxia/reoxygenation injury in vitro and increases graft size and vascularization in vivo. Stem Cells Transl Med 3(6):734–744. doi:10.5966/sctm.2013-0189
Luo J, Weaver MS, Dennis JE et al (2014b) Targeting survival pathways to create infarct-spanning bridges of human embryonic stem cell-derived cardiomyocytes. J Thorac Cardiovasc Surg 148(6):3180-8.e1. doi:10.1016/j.jtcvs.2014.06.087
Makkar RR, Smith RR, Cheng K et al (2012) Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379(9819):895–904. doi:10.1016/S0140-6736(12)60195-0
Malliaras K, Makkar RR, Smith RR et al (2014) 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 63(2):110–122. doi:10.1016/j.jacc.2013.08.724
Matsuo T, Masumoto H, Tajima S et al (2015) Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells. Sci Rep 5:16842. doi:10.1038/srep16842
Matsuura K, Wada H, Nagai T et al (2004) Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle. J Cell Biol 167(2):351–363. doi:10.1083/jcb.200312111
Matsuura K, Kodama F, Sugiyama K et al (2015) Elimination of remaining undifferentiated induced pluripotent stem cells in the process of human cardiac cell sheet fabrication using a methionine-free culture condition. Tissue Eng Part C Methods 21(3):330–338. doi:10.1089/ten.TEC.2014.0198
McLenachan S, Menchon C, Raya A et al (2012) Cyclin A1 is essential for setting the pluripotent state and reducing tumorigenicity of induced pluripotent stem cells. Stem Cells Dev 21(15):2891–2899. doi:10.1089/scd.2012.0190
Mehta A, Chung YY, Ng A et al (2011) Pharmacological response of human cardiomyocytes derived from virus-free induced pluripotent stem cells. Cardiovasc Res 91(4):577–586. doi:10.1093/cvr/cvr132
Meijer van Putten RM, Mengarelli I, Guan K et al (2015) Ion channelopathies in human induced pluripotent stem cell derived cardiomyocytes: a dynamic clamp study with virtual IK1. Front Physiol 6:7. doi:10.3389/fphys.2015.00007
Menasche P, Alfieri O, Janssens S et al (2008) The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 117(9):1189–1200. doi:10.1161/CIRCULATIONAHA.107.734103
Menasche P, Vanneaux V, Fabreguettes JR et al (2015a) Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience. Eur Heart J 36(12):743–750. doi:10.1093/eurheartj/ehu192
Menasche P, Vanneaux V, Hagege A et al (2015b) Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J 36(30):2011–2017. doi:10.1093/eurheartj/ehv189
Menendez S, Camus S, Herreria A et al (2012) Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency. Aging Cell 11(1):41–50. doi:10.1111/j.1474-9726.2011.00754.x
Mihic A, Li J, Miyagi Y et al (2014) The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes. Biomaterials 35(9):2798–2808. doi:10.1016/j.biomaterials.2013.12.052
Mirotsou M, Jayawardena TM, Schmeckpeper J et al (2011) Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 50(2):280–289. doi:10.1016/j.yjmcc. 2010.08.005
Miyagawa S, Sawa Y, Sakakida S et al (2005) Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium. Transplantation 80(11):1586–1595
Molne J, Bjorquist P, Andersson K et al (2008) Blood group ABO antigen expression in human embryonic stem cells and in differentiated hepatocyte- and cardiomyocyte-like cells. Transplantation 86(10):1407–1413. doi:10.1097/TP.0b013e31818a6805
Moon SH, Kang SW, Park SJ et al (2013) The use of aggregates of purified cardiomyocytes derived from human ESCs for functional engraftment after myocardial infarction. Biomaterials 34(16):4013–4026. doi:10.1016/j.biomaterials.2013.02.022
Moore JC, Fu J, Chan YC et al (2008) Distinct cardiogenic preferences of two human embryonic stem cell (hESC) lines are imprinted in their proteomes in the pluripotent state. Biochem Biophys Res Commun 372(4):553–558. doi:10.1016/j.bbrc. 2008.05.076
Mummery C, Ward-van Oostwaard D, Doevendans P et al (2003) Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation 107(21):2733–2740. doi:10.1161/01.CIR.0000068356.38592.68
Murry CE, Wiseman RW, Schwartz SM et al (1996) Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 98(11):2512–2523. doi:10.1172/JCI119070
Murry CE, Soonpaa MH, Reinecke H et al (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428(6983):664–668. doi:10.1038/nature02446
Murry CE, Reinecke H, Pabon LM (2006) Regeneration gaps: observations on stem cells and cardiac repair. J Am Coll Cardiol 47(9):1777–1785. doi:10.1016/j.jacc.2006.02.002
Nabauer M, Beuckelmann DJ, Uberfuhr P et al (1996) Regional differences in current density and rate-dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle. Circulation 93(1):168–177
Nagaya N, Fujii T, Iwase T et al (2004) 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 287(6):H2670–H2676. doi:10.1152/ajpheart.01071.2003
Naito H, Nishizaki K, Yoshikawa M et al (2004) Xenogeneic embryonic stem cell-derived cardiomyocyte transplantation. Transplant Proc 36(8):2507–2508. doi:10.1016/j.transproceed.2004.06.031
Naito AT, Shiojima I, Akazawa H et al (2006) Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis. Proc Natl Acad Sci U S A 103(52):19812–19817. doi:10.1073/pnas.0605768103
Nakajima F, Tokunaga K, Nakatsuji N (2007) Human leukocyte antigen matching estimations in a hypothetical bank of human embryonic stem cell lines in the Japanese population for use in cell transplantation therapy. Stem Cells 25(4):983–985. doi:10.1634/stemcells.2006-0566
Nam YJ, Song K, Luo X et al (2013) Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci U S A 110(14):5588–5593. doi:10.1073/pnas.1301019110
Norol F, Bonnet N, Peinnequin A et al (2007) GFP-transduced CD34+ and Lin- CD34- hematopoietic stem cells did not adopt a cardiac phenotype in a nonhuman primate model of myocardial infarct. Exp Hematol 35(4):653–661. doi:10.1016/j.exphem. 2006.12.003
Nunes SS, Miklas JW, Liu J et al (2013) Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods 10(8):781–787. doi:10.1038/nmeth.2524
Nussbaum J, Minami E, Laflamme MA et al (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J 21(7):1345–1357. doi:10.1096/fj.06-6769com
Oberwallner B, Brodarac A, Choi YH et al (2014) Preparation of cardiac extracellular matrix scaffolds by decellularization of human myocardium. J Biomed Mater Res A 102(9):3263–3272. doi:10.1002/jbma.35000
Otsuji TG, Minami I, Kurose Y et al (2010) Progressive maturation in contracting cardiomyocytes derived from human embryonic stem cells: qualitative effects on electrophysiological responses to drugs. Stem Cell Res 4(3):201–213. doi:10.1016/j.scr.2010.01.002
Ott HC, Matthiesen TS, Goh SK et al (2008) Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med 14(2):213–221. doi:10.1038/nm1684
Paige SL, Osugi T, Afanasiev OK et al (2010) Endogenous Wnt/beta-catenin signaling is required for cardiac differentiation in human embryonic stem cells. PLoS One 5(6):e11134. doi:10.1371/journal.pone.0011134
Pasumarthi KB, Field LJ (2002) Cardiomyocyte cell cycle regulation. Circ Res 90(10):1044–1054
Piacentino V III, Weber CR, Chen X et al (2003) Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ Res 92(6):651–658. doi:10.1161/01.RES.0000062469.83985.9B
Ponten A, Walsh S, Malan D et al (2013) FACS-based isolation, propagation and characterization of mouse embryonic cardiomyocytes based on VCAM-1 surface marker expression. PLoS One 8(12):e82403. doi:10.1371/journal.pone.0082403
Porrello ER, Mahmoud AI, Simpson E et al (2011) Transient regenerative potential of the neonatal mouse heart. Science 331(6020):1078–1080. doi:10.1126/science.1200708
Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298(5601):2188–2190. doi:10.1126/science.1077857
Prowse AB, Timmins NE, Yau TM et al (2014) Transforming the promise of pluripotent stem cell-derived cardiomyocytes to a therapy: challenges and solutions for clinical trials. Can J Cardiol 30(11):1335–1349. doi:10.1016/j.cjca.2014.08.005
Pumir A, Arutunyan A, Krinsky V et al (2005) Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity. Biophys J 89(4):2332–2349. doi:10.1529/biophysj.105.061820
Qian L, Huang Y, Spencer CI et al (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485(7400):593–598. doi:10.1038/nature11044
Qian L, Berry EC, Fu JD et al (2013) Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro. Nat Protoc 8(6):1204–1215. doi:10.1038/nprot.2013.067
Reinecke H, Zhang M, Bartosek T et al (1999) Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation 100(2):193–202
Reinecke H, Poppa V, Murry CE (2002) Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. J Mol Cell Cardiol 34(2):241–249. doi:10.1006/jmcc. 2001.1507
Reinecke H, Robey TE, Mignone JL et al (2013) Lack of thrombospondin-2 reduces fibrosis and increases vascularity around cardiac cell grafts. Cardiovasc Pathol 22(1):91–95. doi:10.1016/j.carpath.2012.03.005
Revazova ES, Turovets NA, Kochetkova OD et al (2007) Patient-specific stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells 9(3):432–449. doi:10.1089/clo.2007.0033
Riegler J, Tiburcy M, Ebert A et al (2015) Human engineered heart muscles engraft and survive long-term in a rodent myocardial infarction model. Circ Res 117(8):720–730. doi:10.1161/CIRCRESAHA.115.306985
Robertson C, Tran DD, George SC (2013) Concise review: maturation phases of human pluripotent stem cell-derived cardiomyocytes. Stem Cells 31(5):829–837. doi:10.1002/stem.1331
Robertson MJ, Dries-Devlin JL, Kren SM et al (2014) Optimizing recellularization of whole decellularized heart extracellular matrix. PLoS One 9(2):e90406. doi:10.1371/journal.pone.0090406
Robey TE, Saiget MK, Reinecke H et al (2008) Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 45(4):567–581. doi:10.1016/j.yjmcc.2008.03.009
Rodriguez ML, Graham BT, Pabon LM et al (2014) Measuring the contractile forces of human induced pluripotent stem cell-derived cardiomyocytes with arrays of microposts. J Biomech Eng 136(5):051005. doi:10.1115/1.4027145
Roell W, Lewalter T, Sasse P et al (2007) Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450(7171):819–824. doi:10.1038/nature06321
Rogers NT, Hobson E, Pickering S et al (2004) Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic activation of human oocytes. Reproduction 128(6):697–702. doi:10.1530/rep.1.00484
Rong Z, Wang M, Hu Z et al (2014) An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell 14(1):121–130. doi:10.1016/j.stem.2013.11.014
Ruan JL, Tulloch NL, Saiget M et al (2015) Mechanical stress promotes maturation of human myocardium from pluripotent stem cell-derived progenitors. Stem Cells 33(7):2148–2157. doi:10.1002/stem.2036
Rubart M, Pasumarthi KB, Nakajima H et al (2003) Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ Res 92(11):1217–1224. doi:10.1161/01.RES.0000075089.39335.8C
Sadat K, Ather S, Aljaroudi W et al (2014) The effect of bone marrow mononuclear stem cell therapy on left ventricular function and myocardial perfusion. J Nucl Cardiol 21(2):351–367. doi:10.1007/s12350-013-9846-4
Sartiani L, Bettiol E, Stillitano F et al (2007) Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach. Stem Cells 25(5):1136–1144. doi:10.1634/stemcells.2006-0466
Satin J, Kehat I, Caspi O et al (2004) Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes. J Physiol 559(Pt 2):479–496. doi:10.1113/jphysiol.2004.068213
Schaper J, Meiser E, Stammler G (1985) Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice, and from human hearts. Circ Res 56(3):377–391
Scorsin M, Hagege AA, Marotte F et al (1997) Does transplantation of cardiomyocytes improve function of infarcted myocardium? Circulation 96(9 Suppl):II-188–II-193
Scorsin M, Hagege A, Vilquin JT et al (2000) Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg 119(6):1169–1175. doi:10.1067/mtc.2000.104865
Sekine H, Shimizu T, Yang J et al (2006) Pulsatile myocardial tubes fabricated with cell sheet engineering. Circulation 114(1 Suppl):I87–I93. doi:10.1161/CIRCULATIONAHA.105.000273
Sekine H, Shimizu T, Hobo K et al (2008) Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances neovascularization and improves cardiac function of ischemic hearts. Circulation 118(14 Suppl):S145–S152. doi:10.1161/CIRCULATIONAHA.107.757286
Sekiya S, Shimizu T, Yamato M et al (2006) Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential. Biochem Biophys Res Commun 341(2):573–582. doi:10.1016/j.bbrc.2005.12.217
Sharma S, Raman S, Sun B et al (2011) Anterior wall viability and low ejection fraction predict functional improvement after CABG. J Surg Res 171(2):416–421. doi:10.1016/j.jss.2010.03.068
Sheng X, Reppel M, Nguemo F et al (2012) Human pluripotent stem cell-derived cardiomyocytes: response to TTX and lidocain reveals strong cell to cell variability. PLoS One 7(9):e45963. doi:10.1371/journal.pone.0045963
Shevach M, Soffer-Tsur N, Fleischer S et al (2014) Fabrication of omentum-based matrix for engineering vascularized cardiac tissues. Biofabrication 6(2). doi:10.1088/1758-5082/6/2/024101
Shiba Y, Fernandes S, Zhu WZ et al (2012) Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature 489(7415):322–325. doi:10.1038/nature11317
Shiba Y, Filice D, Fernandes S et al (2014) Electrical integration of human embryonic stem cell-derived cardiomyocytes in a guinea pig chronic infarct model. J Cardiovasc Pharmacol Ther 19(4):368–381. doi:10.1177/1074248413520344
Shimizu T, Yamato M, Isoi Y et al (2002) Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res 90(3):e40
Shiotani M, Harada T, Abe J et al (2007) Methodological validation of an existing telemetry system for QT evaluation in conscious guinea pigs. J Pharmacol Toxicol Methods 55(1):27–34. doi:10.1016/j.vascn.2006.04.008
Simari RD, Pepine CJ, Traverse JH et al (2014) Bone marrow mononuclear cell therapy for acute myocardial infarction: a perspective from the cardiovascular cell therapy research network. Circ Res 114(10):1564–1568. doi:10.1161/CIRCRESAHA.114.303720
Skobel E, Schuh A, Schwarz ER et al (2004) Transplantation of fetal cardiomyocytes into infarcted rat hearts results in long-term functional improvement. Tissue Eng 10(5–6):849–864. doi:10.1089/1076327041348491
Snir M, Kehat I, Gepstein A et al (2003) Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes. Am J Physiol Heart Circ Physiol 285(6):H2355–H2363. doi:10.1152/ajpheart.00020.2003
Solomon S, Pitossi F, Rao MS (2015) Banking on iPSC--is it doable and is it worthwhile. Stem Cell Rev 11(1):1-10. doi:10.1007/s12015-014-9574-4
Stelzer Y, Yanuka O, Benvenisty N (2011) Global analysis of parental imprinting in human parthenogenetic induced pluripotent stem cells. Nat Struct Mol Biol 18(6):735–741. doi:10.1038/nsmb.2050
Stoppel WL, Hu D, Domian IJ et al (2015) Anisotropic silk biomaterials containing cardiac extracellular matrix for cardiac tissue engineering. Biomed Mater 10(3):034105-6041/10/3/034105. doi:10.1088/1748-6041/10/3/034105
Sun N, Yazawa M, Liu J et al (2012) Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Sci Transl Med 4(130):130ra47. doi:10.1126/scitranslmed.3003552
Swoap SJ, Overton JM, Garber G (2004) Effect of ambient temperature on cardiovascular parameters in rats and mice: a comparative approach. Am J Phys Regul Integr Comp Phys 287(2):R391–R396. doi:10.1152/ajpregu.00731.2003
Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. doi:10.1016/j.cell.2007.11.019
Tang YL, Zhao Q, Zhang YC et al (2004) Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept 117(1):3–10
Tannenbaum SE, Turetsky TT, Singer O et al (2012) Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications. PLoS One 7(6):e35325. doi:10.1371/journal.pone.0035325
Taylor DA, Atkins BZ, Hungspreugs P et al (1998) Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4(8):929–933
Taylor CJ, Bolton EM, Pocock S et al (2005) Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366(9502):2019–2025. doi:10.1016/S0140-6736(05)67813-0
Taylor RE, Kim K, Sun N et al (2013) Sacrificial layer technique for axial force post assay of immature cardiomyocytes. Biomed Microdevices 15(1):171–181. doi:10.1007/s10544-012-9710-3
Terrenoire C, Wang K, Tung KW et al (2013) Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics. J Gen Physiol 141(1):61–72. doi:10.1085/jgp.201210899
Thavandiran N, Dubois N, Mikryukov A et al (2013) Design and formulation of functional pluripotent stem cell-derived cardiac microtissues. Proc Natl Acad Sci U S A 110(49):E4698–E4707. doi:10.1073/pnas.1311120110
Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147
Tomita S, Li RK, Weisel RD et al (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100(19 Suppl):II247–II256
Tseliou E, de Couto G, Terrovitis J et al (2014) Angiogenesis, cardiomyocyte proliferation and anti-fibrotic effects underlie structural preservation post-infarction by intramyocardially-injected cardiospheres. PLoS One 9(2):e88590. doi:10.1371/journal.pone.0088590
Tulloch NL, Muskheli V, Razumova MV et al (2011) Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 109(1):47–59. doi:10.1161/CIRCRESAHA.110.237206
Turner WS, Wang X, Johnson S et al (2012) Cardiac tissue development for delivery of embryonic stem cell-derived endothelial and cardiac cells in natural matrices. J Biomed Mater Res B Appl Biomater 100(8):2060–2072. doi:10.1002/jbm.b.32770
Ueno S, Weidinger G, Osugi T et al (2007) Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. Proc Natl Acad Sci U S A 104(23):9685–9690. doi:10.1073/pnas.0702859104
Valderrábano M (2007) Influence of anisotropic conduction properties in the propagation of the cardiac action potential. Prog Biophys Mol Biol 94(1–2):144–168. doi:10.1016/j.pbiomolbio.2007.03.014
van der Velden J, Klein LJ, van der Bijl M et al (1999) Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart. Cardiovasc Res 42(3):706–719
Wainwright JM, Czajka CA, Patel UB et al (2010) Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng Part C Methods 16(3):525–532. doi:10.1089/ten.TEC.2009.0392
Wang X, Jameel MN, Li Q et al (2009) Stem cells for myocardial repair with use of a transarterial catheter. Circulation 120(11 Suppl):S238–S246. doi:10.1161/CIRCULATIONAHA.109.885236
Watanabe E, Smith DM Jr, Delcarpio JB et al (1998) Cardiomyocyte transplantation in a porcine myocardial infarction model. Cell Transplant 7(3):239–246
Weisbrod D, Peretz A, Ziskind A et al (2013) SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells. Proc Natl Acad Sci U S A 110(18):E1685–E1694. doi:10.1073/pnas.1221022110
Weng Z, Kong CW, Ren L et al (2014) A simple, cost-effective but highly efficient system for deriving ventricular cardiomyocytes from human pluripotent stem cells. Stem Cells Dev 23(14):1704–1716. doi:10.1089/scd.2013.0509
Weymann A, Patil NP, Sabashnikov A et al (2014) Bioartificial heart: a human-sized porcine model--the way ahead. PLoS One 9(11):e111591. doi:10.1371/journal.pone.0111591
Weymann A, Patil NP, Sabashnikov A et al (2015) Perfusion-decellularization of porcine lung and trachea for respiratory bioengineering. Artif Organs 39(12):1024–1032. doi:10.1111/aor.12481
Witjas-Paalberends ER, Piroddi N, Stam K et al (2013) Mutations in MYH7 reduce the force generating capacity of sarcomeres in human familial hypertrophic cardiomyopathy. Cardiovasc Res 99(3):432–441. doi:10.1093/cvr/cvt119
Xi J, Khalil M, Spitkovsky D et al (2011) Fibroblasts support functional integration of purified embryonic stem cell-derived cardiomyocytes into avital myocardial tissue. Stem Cells Dev 20(5):821–830. doi:10.1089/scd.2010.0398
Xu C, Police S, Rao N et al (2002) Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 91(6):501–508
Xu C, Police S, Hassanipour M et al (2011) Efficient generation and cryopreservation of cardiomyocytes derived from human embryonic stem cells. Regen Med 6(1):53–66. doi:10.2217/rme.10.91
Xu B, Li Y, Fang X et al (2013) Mechanically tissue-like elastomeric polymers and their potential as a vehicle to deliver functional cardiomyocytes. J Mech Behav Biomed Mater 28:354–365. doi:10.1016/j.jmbbm.2013.06.005
Xue T, Cho HC, Akar FG et al (2005) Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 111(1):11–20. doi:10.1161/01.CIR.0000151313.18547.A2
Yang L, Soonpaa MH, Adler ED et al (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453(7194):524–528. doi:10.1038/nature06894
Yang Z, Zhang F, Ma W et al (2010) A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery. Cardiovasc Ther 28(6):380–385. doi:10.1111/j.1755-5922.2009.00116.x
Yang WJ, Li SH, Weisel RD et al (2012) Cell fusion contributes to the rescue of apoptotic cardiomyocytes by bone marrow cells. J Cell Mol Med 16(12):3085–3095. doi:10.1111/j.1582-4934. 2012.01600.x
Yang X, Rodriguez M, Pabon L et al (2014) Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J Mol Cell Cardiol 72:296–304. doi:10.1016/j.yjmcc.2014.04.005
Yang T, Rubart M, Soonpaa MH et al (2015) Cardiac engraftment of genetically-selected parthenogenetic stem cell-derived cardiomyocytes. PLoS One 10(6):e0131511. doi:10.1371/journal.pone.0131511
Yasui H, Lee JK, Yoshida A et al (2014) Excitation propagation in three-dimensional engineered hearts using decellularized extracellular matrix. Biomaterials 35(27):7839–7850. doi:10.1016/j.biomaterials.2014.05.080
Ye L, Chang Y, Xiong Q et al (2014) Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell 15(6):750–761. doi:10.1016/j.stem.2014.11.009
Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920. doi:10.1126/science.1151526
Zhang YM, Hartzell C, Narlow M et al (2002) Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. Circulation 106(10):1294–1299
Zhang J, Wilson GF, Soerens AG et al (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104(4):e30–e41. doi:10.1161/CIRCRESAHA.108.192237
Zhang J, Klos M, Wilson GF et al (2012) Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells: the matrix sandwich method. Circ Res 111(9):1125–1136. doi:10.1161/CIRCRESAHA.112.273144
Zhang XH, Haviland S, Wei H et al (2013a) Ca2+ signaling in human induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) from normal and catecholaminergic polymorphic ventricular tachycardia (CPVT)-afflicted subjects. Cell Calcium 54(2):57–70. doi:10.1016/j.ceca.2013.04.004
Zhang D, Shadrin IY, Lam J et al (2013b) Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials 34(23):5813–5820. doi:10.1016/j.biomaterials.2013.04.026
Zhang L, Pan Y, Qin G et al (2014) Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: improving the safety of iPS cell transplantation to myocardium. Cell Cycle 13(5):762–771. doi:10.4161/cc.27677
Zhou YY, Zeng F (2013) Integration-free methods for generating induced pluripotent stem cells. Genom Proteom Bioinfo 11(5):284–287. doi:10.1016/j.gpb.2013.09.008
Zhu WZ, Santana LF, Laflamme MA (2009) Local control of excitation-contraction coupling in human embryonic stem cell-derived cardiomyocytes. PLoS One 4(4):e5407. doi:10.1371/journal.pone.0005407
Zhu WZ, Xie Y, Moyes KW et al (2010) Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells. Circ Res 107(6):776–786. doi:10.1161/CIRCRESAHA.110.223917
Zhu WZ, Van Biber B, Laflamme MA (2011) Methods for the derivation and use of cardiomyocytes from human pluripotent stem cells. Methods Mol Biol 767:419–431. doi:10.1007/978-1-61779-201-4_31
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants performed by any of the authors. Animal research was performed in accordance with institutional, local, and federal regulations. This work was supported by T32 HL007312 (MEH), Future Leader Fellowship (ID 100463) from the National Heart Foundation of Australia (JJHC) and Sydney Medical School Foundation Fellowship (JJHC), RO1 NIH HL117991 (MAL), and funding from the McEwen Centre for Regenerative Medicine, the Toronto General Hospital Research Institute, the Ontario Institute for Regenerative Medicine, and the Peter Munk Cardiac Centre (MAL).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Hartman, M.E., Chong, J.J.H., Laflamme, M.A. (2017). State of the Art in Cardiomyocyte Transplantation. In: Ieda, M., Zimmermann, WH. (eds) Cardiac Regeneration. Cardiac and Vascular Biology, vol 4. Springer, Cham. https://doi.org/10.1007/978-3-319-56106-6_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-56106-6_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-56104-2
Online ISBN: 978-3-319-56106-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)