Vascularisation for cardiac tissue engineering: the extracellular matrix

Summary

Cardiovascular diseases present a major socio-economic burden. One major problem underlying most cardiovascular and congenital heart diseases is the irreversible loss of contractile heart muscle cells, the cardiomyocytes. To reverse damage incurred by myocardial infarction or by surgical correction of cardiac malformations, the loss of cardiac tissue with a thickness of a few millimetres needs to be compensated. A promising approach to this issue is cardiac tissue engineering. In this review we focus on the problem of in vitro vascularisation as implantation of cardiac patches consisting of more than three layers of cardiomyocytes (> 100 μm thick) already results in necrosis. We explain the need for vascularisation and elaborate on the importance to include non-myocytes in order to generate functional vascularised cardiac tissue. We discuss the potential of extracellular matrix molecules in promoting vascularisation and introduce nephronectin as an example of a new promising candidate. Finally, we discuss current biomaterial- based approaches including micropatterning, electrospinning, 3D micro-manufacturing technology and porogens. Collectively, the current literature supports the notion that cardiac tissue engineering is a realistic option for future treatment of paediatric and adult patients with cardiac disease.

Keywords

Heart - vascularisation - coronary vasculature - tissue engineering - extracellular matrix

• References

• 1 Go AS. et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 2014; 129: e28-e292.
• 2 The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). New Engl J Med 1987; 316: 1429-1435.
• 3 Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311-322.
• 4 Antman EM. et al. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. New Engl J Med 2006; 354: 1477-1488.
• 5 Bardy GH. et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. New Engl J Med 2005; 352: 225-237.
• 6 Brautbar A, Ballantyne CM. Pharmacological strategies for lowering LDL cholesterol: statins and beyond. Nat Rev Cardiol 2011; 8: 253-65.
• 7 Brizzio ME, Zapolanski A. Antiplatelet therapy, cardiac surgery, and the risk of bleeding: the surgeon’s perspective. Rev Cardiovasc Med 2011; 12: S40-46.
• 8 Granger CB. et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-convert-ing-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772-776.
• 9 Nolan CJ. et al. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 2011; 378: 169-181.
• 10 Pitt B. et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomised Aldactone Evaluation Study Investigators. New Engl J Med 1999; 341: 709-717.
• 11 Schomig A. et al. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investigators. New Engl J Med 2000; 343: 385-391.
• 12 Zhao D. et al. Dietary factors associated with hypertension. Nat Rev Cardiol 2011; 8: 456-465.
• 13 van der Linde D. et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 2011; 58: 2241-2247.
• 14 Buja LM. The pathobiology of acute coronary syndromes: clinical implications and central role of the mitochondria. Tex Heart Inst J 2013; 40: 221-228.
• 15 Le Gloan L. et al. Tetralogy of Fallot and aortic root disease. Expert Rev Cardiovasc Ther 2013; 11: 233-238.
• 16 Feinstein JA. et al. Hypoplastic left heart syndrome: current considerations and expectations. J Am Coll Cardiol 2012; 59: S1-42.
• 17 Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress. Circulation 2000; 102: IV14-23.
• 18 Chien KR. Stress pathways and heart failure. Cell 1999; 98: 555-558.
• 19 Heusch G. et al. Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 2014; 383: 1933-1943.
• 20 Krieger EV, Valente AM. Heart failure treatment in adults with congenital heart disease: where do we stand in 2014?. Heart 2014; 100: 1329-1334.
• 21 Dinardo JA. Heart failure associated with adult congenital heart disease. Semin Cardiothorac Vasc Anesth 2013; 17: 44-54.
• 22 Taylor DO. et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report--2008. J Heart Lung Transplant 2008; 27: 943-956.
• 23 Langone AJ, Helderman JH. Disparity between solid-organ supply and demand. New Engl J Med 2003; 349: 704-706.
• 24 Picascia A, Grimaldi V, Zullo A. et al. Current concepts in histocompatibility during heart transplant. Exp Clin Transplant 2012; 10: 209-218.
• 25 Tonsho M. et al. Heart transplantation: challenges facing the field. Cold Spring Harb Perspect Med. 2014 Epub ahead of print.
• 26 Longnus SL. et al. Heart transplantation with donation after circulatory determination of death. Nat Rev Cardiol 2014; 11: 354-363.
• 27 Byrne GW, McGregor CG. Cardiac xenotransplantation: progress and challenges. Curr Opin Organ Transplant 2012; 17: 148-154.
• 28 Ekser B. et al. Xenotransplantation of solid organs in the pig-to-primate model. Transplant Immunol 2009; 21: 87-92.
• 29 Naso F, Gandaglia A, Iop L. et al. Alpha-Gal detectors in xenotransplantation research: a word of caution. Xenotransplantation 2012; 19: 215-220.
• 30 Sluijter JP. et al. Novel Therapeutic Strategies for Cardioprotection. Pharmacol Ther 2014; 144: 60-70.
• 31 Tian T. et al. Intramyocardial autologous bone marrow cell transplantation for ischaemic heart disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis 2014; 233: 485-492.
• 32 Martin-Puig S. et al. Heart repair: from natural mechanisms of cardiomyocyte production to the design of new cardiac therapies. Ann NY Acad Sci 2012; 1254: 71-81.
• 33 Hsieh PC, Segers VF, Davis ME. et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 2007; 13: 970-974.
• 34 Frati C. et al. Resident cardiac stem cells. Curr Pharm Des 2011; 17: 3252-3257.
• 35 Chugh AR. et al. Administration of cardiac stem cells in patients with ischaemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation 2012; 126: S54-64.
• 36 Guo C. et al. Direct somatic cell reprogramming: treatment of cardiac diseases. Curr Gene Ther 2013; 13: 133-138.
• 37 Ieda M. et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010; 142: 375-386.
• 38 Qian L, Srivastava D. Direct cardiac reprogramming: from developmental biology to cardiac regeneration. Circ Res 2013; 113: 915-921.
• 39 Song K. et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 2012; 485: 599-604.
• 40 Engel FB. Cardiomyocyte proliferation: a platform for mammalian cardiac repair. Cell Cycle 2005; 4: 1360-1363.
• 41 van Amerongen MJ, Engel FB. Features of cardiomyocyte proliferation and its potential for cardiac regeneration. J Cell Mol Med 2008; 12: 2233-2244.
• 42 Zebrowski DC, Engel FB. The cardiomyocyte cell cycle in hypertrophy, tissue homeostasis, and regeneration. Rev Physiol Biochem Pharmacol 2013; 165: 67-96.
• 43 Bergmann O. et al. Evidence for cardiomyocyte renewal in humans. Science 2009; 324: 98-102.
• 44 Hirt MN, Hansen A, Eschenhagen T. Cardiac tissue engineering: state of the art. Circ Res 2014; 114: 354-367.
• 45 Couzin-Frankel J. The elusive heart fix. Science 2014; 345: 252-257.
• 46 Servick K. Top heart lab comes under fire. Science 2014; 345: 254.
• 47 Banerjee I. et al. Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse. Am J Physiol Heart Circ Physiol 2007; 293: H1883-1891.
• 48 Chottova Dvorakova M. et al. Expression of neuropeptide Y and its receptors Y1 and Y2 in the rat heart and its supplying autonomic and spinal sensory ganglia in experimentally induced diabetes. Neuroscience 2008; 151: 1016-1028.
• 49 Higuchi K. et al. Scanning electron microscopic studies of the vascular smooth muscle cells and pericytes in the rat heart. Arch Histol Cytol 2000; 63: 115-126.
• 50 Pauziene N. et al. Morphology of human intracardiac nerves: an electron microscope study. J Anat 2000; 197: 437-459.
• 51 Vliegen HW. et al. Myocardial changes in pressure overload-induced left ventricular hypertrophy. A study on tissue composition, polyploidisation and multinucleation. Eur Heart J 1991; 12: 488-494.
• 52 Boukens BJ. et al. Developmental basis for electrophysiological heterogeneity in the ventricular and outflow tract myocardium as a substrate for life-threatening ventricular arrhythmias. Circ Res 2009; 104: 19-31.
• 53 Hoogaars WM. et al. T-box factors determine cardiac design. Cell Mol Life Sci 2007; 64: 646-660.
• 54 Moorman AF, Christoffels VM. Cardiac chamber formation: development, genes, and evolution. Physiol Rev 2003; 83: 1223-1267.
• 55 Coghlan HC. et al. The structure and function of the helical heart and its buttress wrapping. III. The electric spiral of the heart: The hypothesis of the anisot-ropic conducting matrix. Semin Thorac Cardiovasc Surg 2001; 13: 333-341.
• 56 Torrent-Guasp F. et al. The structure and function of the helical heart and its buttress wrapping. I. The normal macroscopic structure of the heart. Semin Thorac Cardiovasc Surg 2001; 13: 301-319.
• 57 Fomovsky GM. et al. Contribution of extracellular matrix to the mechanical properties of the heart. J Mol Cell Cardiol 2010; 48: 490-496.
• 58 Reffelmann T. et al. Cardiomyocyte transplantation into the failing heart-new therapeutic approach for heart failure?. Heart Fail Rev 2003; 8: 201-211.
• 59 Pasumarthi KB. et al. Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice. Circ Res 2005; 96: 110-118.
• 60 Zimmermann WH, Melnychenko I, Wasmeier G. et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 2006; 12: 452-458.
• 61 Poss KD. et al. Heart regeneration in zebrafish. Science 2002; 298: 2188-2190.
• 62 Porrello ER. et al. Transient regenerative potential of the neonatal mouse heart. Science 2011; 331: 1078-1080.
• 63 Kikuchi K. et al. Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell 2011; 20: 397-404.
• 64 Zhao L. et al. Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Proc Natl Acad Sci U S A 2014; 111: 1403-1408.
• 65 Kim J. et al. PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. Proc Natl Acad Sci USA 2010; 107: 17206-17210.
• 66 Yang Y. et al. VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells. J Appl Physiol 2002; 93: 1140-1151.
• 67 Naito H. et al. Optimising engineered heart tissue for therapeutic applications as surrogate heart muscle. Circulation 2006; 114: I72-178.
• 68 Radisic M. et al. Cardiac tissue engineering using perfusion bioreactor systems. Nat Protoc 2008; 3: 719-738.
• 69 Kensah G. et al. Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro. Eur Heart J 2013; 34: 1134-1146.
• 70 Tulloch NL. et al. Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 2011; 109: 47-59.
• 71 Lesman A. et al. Transplantation of a tissue-engineered human vascularised cardiac muscle. Tissue Eng Part A 2010; 16: 115-125.
• 72 Caspi O. et al. Tissue engineering of vascularised cardiac muscle from human embryonic stem cells. Circ Res 2007; 100: 263-272.
• 73 Newman AC. et al. The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix proteins are essential for endothelial cell lumen formation. Mol Bio Cell 2011; 22: 3791-3800.
• 74 Zeng QC. et al. Cardiac fibroblast-derived extracellular matrix produced in vitro stimulates growth and metabolism of cultured ventricular cells. Int Heart J 2013; 54: 40-44.
• 75 Korecky B. et al. Functional capillary density in normal and transplanted rat hearts. Can J Physiol Pharmacol 1982; 60: 23-32.
• 76 Rakusan K. et al. Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy. Circulation 1992; 86: 38-46.
• 77 Matsuura K. et al. Toward the development of bioengineered human three-dimensional vascularised cardiac tissue using cell sheet technology. Int Heart J 2014; 55: 1-7.
• 78 Shimizu T. et al. Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick, vascularised myocardial tissues. FASEB J 2006; 20: 708-710.
• 79 Shimizu T. et al. Cell sheet engineering for myocardial tissue reconstruction. Biomaterials 2003; 24: 2309-2316.
• 80 Acarturk TO. et al. Laparoscopically harvested omental flap for chest wall and intrathoracic reconstruction. Ann Plast Surg 2004; 53: 210-216.
• 81 Panaro F. et al. Omental Flap for Hepatic Artery Coverage During Liver Transplantation. J Gastrointest Surg. 2014; 18: 1518-1522.
• 82 Kawamura M. et al. Enhanced survival of transplanted human induced pluripotent stem cell-derived cardiomyocytes by the combination of cell sheets with the pedicled omental flap technique in a porcine heart. Circulation 2013; 128: S87-94.
• 83 Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005; 438: 932-936.
• 84 Yancopoulos GD. et al. Vascular-specific growth factors and blood vessel formation. Nature 2000; 407: 242-248.
• 85 Olivey HE, Svensson EC. Epicardial-myocardial signaling directing coronary vasculogenesis. Circ Res 2010; 106: 818-832.
• 86 Ratajska A. et al. Embryonic development of the proepicardium and coronary vessels. Int J Dev Biol 2008; 52: 229-236.
• 87 Tian X. et al. Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries. Cell Res 2013; 23: 1075-1090.
• 88 Potente M. et al. Basic and therapeutic aspects of angiogenesis. Cell 2011; 146: 873-887.
• 89 Segura I. et al. The neurovascular link in health and disease: an update. Trends Mol Med 2009; 15: 439-451.
• 90 Welti J. et al. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest 2013; 123: 3190-3200.
• 91 Arroyo AG, Iruela-Arispe ML. Extracellular matrix, inflammation, and the angiogenic response. Cardiovasc Res 2010; 86: 226-235.
• 92 Davies JE, Sundt TM. Surgery insight: the dilated ascending aorta--indications for surgical intervention. Nat Clin Pract Cardiovasc Med 2007; 4: 330-339.
• 93 Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev 1990; 70: 921-961.
• 94 Lammert E, Axnick J. Vascular lumen formation. Cold Spring Harb Perspect Med 2012; 2: a006619.
• 95 Gittenberger-de Groot AC. et al. Smooth muscle cell origin and its relation to heterogeneity in development and disease. Arterioscler Thromb Vasc Biol 1999; 19: 1589-1594.
• 96 Rizzoni D. et al. Vascular remodeling, macro- and microvessels: therapeutic implications. Blood Press 2009; 18: 242-246.
• 97 Pries AR, Kuebler WM. Normal endothelium. Handb Exp Pharmacol 2006; 176: 1-40.
• 98 Risau W. Development and differentiation of endothelium. Kidney Int Suppl 1998; 67: S3-6.
• 99 Satchell S. The role of the glomerular endothelium in albumin handling. Nat Rev Nephrol 2013; 9: 717-725.
• 100 DeLeve LD. et al. Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation. Am J Physiol Gastrointest Liver Physiol 2004; 287: G757-763.
• 101 Feigl EO. Coronary physiology. Physiol Rev 1983; 63: 1-205.
• 102 Echeverri D. et al. Myocardial venous drainage: from anatomy to clinical use. J Invasive Cardiol 2013; 25: 98-105.
• 103 Westerhof N. et al. Cross-talk between cardiac muscle and coronary vasculature. Physiol Rev 2006; 86: 1263-1308.
• 104 Zimmermann WH, Cesnjevar R. Cardiac tissue engineering: implications for pediatric heart surgery. Pediatr Cardiol 2009; 30: 716-723.
• 105 Dai W. et al. Thickening of the infarcted wall by collagen injection improves left ventricular function in rats: a novel approach to preserve cardiac function after myocardial infarction. J Am Coll Cardiol 2005; 46: 714-719.
• 106 Jiang XJ. et al. Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction. J Biomed Mater Res A 2009; 90: 472-477.
• 107 Matsa E. et al. Cardiac stem cell biology: glimpse of the past, present, and future. Circ Res 2014; 114: 21-27.
• 108 Messina E. et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 2004; 95: 911-921.
• 109 Pavo N. et al. Cell therapy for human ischaemic heart diseases: Critical review and summary of the clinical experiences. J Mol Cell Cardiol 2014; 75: 12-24.
• 110 Vunjak-Novakovic G. et al. Challenges in cardiac tissue engineering. Tissue Eng Part B Rev 2010; 16: 169-187.
• 111 Pincott ES, Burch M. Potential for stem cell use in congenital heart disease. Future Cardiol 2012; 8: 161-169.
• 112 Kalfa D, Bacha E. New technologies for surgery of the congenital cardiac defect. Rambam Maimonides Med J 2013; 4: e0019.
• 113 Tiburcy M. et al. Terminal differentiation, advanced organotypic maturation, and modeling of hypertrophic growth in engineered heart tissue. Circ Res 2011; 109: 1105-1114.
• 114 Ciubotaru A. et al. Biological heart valves. Biomed Tech 2013; 58: 389-397.
• 115 Schoen FJ. Heart valve tissue engineering: quo vadis?. Curr Opin Biotechnol 2011; 22: 698-705.
• 116 Zimmermann WH. et al. Tissue engineering of a differentiated cardiac muscle construct. Circ Res 2002; 90: 223-230.
• 117 Stevens KR. et al. Physiological function and transplantation of scaffold-free and vascularised human cardiac muscle tissue. Proc Natl Acad Sci USA 2009; 106: 16568-16573.
• 118 Sekine H. et al. Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances neovascularisation and improves cardiac function of ischaemic hearts. Circulation 2008; 118: S145-152.
• 119 Radisic M. et al. Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. Am J Physiol Heart Circ Physiol 2005; 288: H1278-1289.
• 120 Dvir T. et al. Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes cardiac tissue assembly. Tissue Eng 2007; 13: 2185-2193.
• 121 Montgomery M. et al. Cardiac Tissue Vascularisation: From Angiogenesis to Microfluidic Blood Vessels. J Cardiovasc Pharmacol Ther 2014; 19: 382-393.
• 122 Boland ED. et al. Electrospinning collagen and elastin: preliminary vascular tissue engineering. Front Biosci 2004; 9: 1422-1432.
• 123 Zheng Y. et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proc Natl Acad Sci USA 2012; 109: 9342-9347.
• 124 Wray LS. et al. Slowly degradable porous silk microfabricated scaffolds for vascularised tissue formation. Adv Funct Mater 2013; 23: 3404-3412.
• 125 Dolati F. et al. In vitro evaluation of carbon-nanotube-reinforced bioprintable vascular conduits. Nanotechnology 2014; 25: 145101.
• 126 Baranski JD. et al. Geometric control of vascular networks to enhance engineered tissue integration and function. Proc Natl Acad Sci USA 2013; 110: 7586-7591.
• 127 Beier JP. et al. De novo generation of axially vascularised tissue in a large animal model. Microsurgery 2009; 29: 42-51.
• 128 Morritt AN. et al. Cardiac tissue engineering in an in vivo vascularised chamber. Circulation 2007; 115: 353-360.
• 129 Matsuda K. et al. Adipose-derived stem cells promote angiogenesis and tissue formation for in vivo tissue engineering. Tissue Eng Part A 2013; 19: 1327-1335.
• 130 Tee R. et al. Transplantation of engineered cardiac muscle flaps in syngeneic rats. Tissue Eng Part A 2012; 18: 1992-1999.
• 131 Sekine H. et al. In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat Commun 2013; 4: 1399.
• 132 Chiu LL. et al. Perfusable branching microvessel bed for vascularisation of engineered tissues. Proc Natl Acad Sci USA 2012; 109: E3414-3423.
• 133 Zieber L. et al. Microfabrication of channel arrays promotes vessel-like network formation in cardiac cell construct and vascularisation in vivo. Biofabrication 2014; 6: 024102.
• 134 Radisic M. et al. Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue. J Biomed Mater Res A 2008; 86: 713-724.
• 135 Radisic M. et al. Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds. Tissue Eng 2006; 12: 2077-2091.
• 136 Gacche RN, Meshram RJ. Angiogenic factors as potential drug target: Efficacy and limitations of anti-angiogenic therapy. Biochim Biophys Acta 2014; 1846: 161-179.
• 137 Mittal K. et al. Angiogenesis and the tumor microenvironment: vascular endothelial growth factor and beyond. Semin Oncol 2014; 41: 235-251.
• 138 Yoo SY, Kwon SM. Angiogenesis and its therapeutic opportunities. Mediators Inflamm 2013; 2013: 127170.
• 139 Geudens I, Gerhardt H. Coordinating cell behaviour during blood vessel formation. Development 2011; 138: 4569-4583.
• 140 Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473: 298-307.
• 141 Fagiani E, Christofori G. Angiopoietins in angiogenesis. Cancer Lett 2013; 328: 18-26.
• 142 Murakami M. et al. Non-canonical fibroblast growth factor signalling in angiogenesis. Cardiovasc Res 2008; 78: 223-231.
• 143 Nakayama M. et al. Spatial regulation of VEGF receptor endocytosis in angiogenesis. Nat Cell Biol 2013; 15: 249-260.
• 144 Ramsauer M, D‘Amore PA. Contextual role for angiopoietins and TGFbeta1 in blood vessel stabilisation. J Cell Sci 2007; 120: 1810-1817.
• 145 Lavine KJ, Ornitz DM. Rebuilding the coronary vasculature: hedgehog as a new candidate for pharmacologic revascularisation. Trends Cardiovasc Med 2007; 17: 77-83.
• 146 Lavine KJ, Ornitz DM. Shared circuitry: developmental signaling cascades regulate both embryonic and adult coronary vasculature. Circ Res 2009; 104: 159-169.
• 147 Ferrari R, Rizzo P. The Notch pathway: a novel target for myocardial remodelling therapy?. Eur Heart J 2014; 35: 2140-2145.
• 148 Kaminsky SM. et al. Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease. Hum Gene Ther 2013; 24: 948-963.
• 149 Lokmic Z, Mitchell GM. Engineering the microcirculation. Tissue Eng Part B Rev 2008; 14: 87-103.
• 150 Ozawa CR. et al. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest 2004; 113: 516-527.
• 151 Tiruvannamalai-Annamalai R. et al. A glycosaminoglycan based, modular tissue scaffold system for rapid assembly of perfusable, high cell density, engineered tissues. PloS One 2014; 9: e84287.
• 152 Bian W. et al. Controlling the structural and functional anisotropy of engineered cardiac tissues. Biofabrication 2014; 6: 024109.
• 153 Engelmayr Jr. GC. et al. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat Mater 2008; 7: 1003-1010.
• 154 Ravichandran R. et al. Poly(Glycerol sebacate)/gelatin core/shell fibrous structure for regeneration of myocardial infarction. Tissue Eng Part A 2011; 17: 1363-1373.
• 155 Madden LR. et al. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc Natl Acad Sci USA 2010; 107: 15211-15216.
• 156 Boffito M. et al. Polymeric scaffolds for cardiac tissue engineering: requirements and fabrication technologies. Polym Int 2014; 63: 2-11.
• 157 Jawad H. et al. Myocardial tissue engineering: a review. J Tissue Eng Regen Med 2007; 1: 327-342.
• 158 Chen QZ. et al. An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart. Biomaterials 2010; 31: 3885-3893.
• 159 Ravichandran R. et al. Expression of cardiac proteins in neonatal cardiomyocytes on PGS/fibrinogen core/shell substrate for Cardiac tissue engineering. Int J Cardiol 2013; 167: 1461-1468.
• 160 Kolewe ME. et al. 3D structural patterns in scalable, elastomeric scaffolds guide engineered tissue architecture. Adv Mater 2013; 25: 4459-4465.
• 161 Rotenberg MY. et al. A multi-shear perfusion bioreactor for investigating shear stress effects in endothelial cell constructs. Lab Chip 2012; 12: 2696-2703.
• 162 Kang TY, Hong JM, Kim BJ. et al. Enhanced endothelialisation for developing artificial vascular networks with a natural vessel mimicking the luminal surface in scaffolds. Acta Biomater 2013; 9: 4716-4725.
• 163 Pagliari S. et al. A multistep procedure to prepare pre-vascularised cardiac tissue constructs using adult stem sells, dynamic cell cultures, and porous scaffolds. Front Physiol 2014; 5: 210.
• 164 Gonfiotti A. et al. The first tissue-engineered airway transplantation: 5-year follow-up results. Lancet 2014; 383: 238-244.
• 165 Hibino N. et al. Late-term results of tissue-engineered vascular grafts in humans. J Thorac Cardiovasc Surg 2010; 139: 431-6 6 e1-2.
• 166 Atala A. et al. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 2006; 367: 1241-1246.
• 167 Beltrami CA. et al. Structural basis of end-stage failure in ischaemic cardiomyopathy in humans. Circulation 1994; 89: 151-163.
• 168 Harnarayan C. et al. Quantitative study of infarcted myocardium in cardiogenic shock. B Heart J 1970; 32: 728-732.
• 169 Ferreira R. The reduction of infarct size—forty years of research. Rev Port Cardiol 2010; 29: 1037-1053.
• 170 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
• 171 Fu X. The immunogenicity of cells derived from induced pluripotent stem cells. Cell Mol Immunol 2014; 11: 14-16.
• 172 Guha P. et al. Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell 2013; 12: 407-412.
• 173 Zhao T. et al. Immunogenicity of induced pluripotent stem cells. Nature 2011; 474: 212-215.
• 174 Cao J. et al. Cells derived from iPSC can be immunogenic - yes or no?. Protein Cell 2014; 5: 1-3.
• 175 Didie M. et al. Parthenogenetic stem cells for tissue-engineered heart repair. J Clin Invest 2013; 123: 1285-1298.
• 176 Hiura H, Toyoda M, Okae H. et al. Stability of genomic imprinting in human induced pluripotent stem cells. BMC Genet 2013; 14: 32.
• 177 Martins-Taylor K, Xu RH. Concise review: Genomic stability of human induced pluripotent stem cells. Stem Cells 2012; 30: 22-27.
• 178 Panopoulos AD. et al. iPSCs: induced back to controversy. Cell Stem Cell 2011; 8: 347-348.
• 179 Park H. et al. Increased genomic integrity of an improved protein-based mouse induced pluripotent stem cell method compared with current viral-induced strategies. Stem Cells Transl Med 2014; 3: 599-609.
• 180 Pera MF. Stem cells: The dark side of induced pluripotency. Nature 2011; 471: 46-47.
• 181 Babiarz JE. et al. Determination of the human cardiomyocyte mRNA and miRNA differentiation network by fine-scale profiling. Stem Cells Dev 2012; 21: 1956-1965.
• 182 Yang X. et al. Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes. Circ Res 2014; 114: 511-523.
• 183 Eschenhagen T. et al. Physiological aspects of cardiac tissue engineering. Am J Physiol Heart Circ Physiol 2012; 303: H133-143.
• 184 Hasenfuss G. et al. Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species. Circ Res 1991; 68: 836-846.
• 185 Kim S, von Recum H. Endothelial stem cells and precursors for tissue engineering: cell source, differentiation, selection, and application. Tissue Eng Part B Rev 2008; 14: 133-147.
• 186 Atluri P. et al. Normalisation of postinfarct biomechanics using a novel tissue-engineered angiogenic construct. Circulation 2013; 128: S95-104.
• 187 Suzuki H. et al. Comparative angiogenic activities of induced pluripotent stem cells derived from young and old mice. PloS One 2012; 7: e39562.
• 188 Takebe T. et al. Generation of functional human vascular network. Transplant Proc 2012; 44: 1130-1133.
• 189 Zhang L, Xu Q. Stem/Progenitor cells in vascular regeneration. Arterioscler Thromb Vasc Biol 2014; 34: 1114-1119.
• 190 Edelman DA. et al. Pericytes and their role in microvasculature homeostasis. J Surg Res 2006; 135: 305-311.
• 191 Hirschi KK, D‘Amore PA. Pericytes in the microvasculature. Cardiovasc Res 1996; 32: 687-698.
• 192 Aydin S. et al. The cardiovascular system and the biochemistry of grafts used in heart surgery. Springerplus 2013; 2: 612.
• 193 Ghista DN, Kabinejadian F. Coronary artery bypass grafting hemodynamics and anastomosis design: a biomedical engineering review. Biomed Eng Online 2013; 12: 129.
• 194 Busch R. et al. New stent surface materials: the impact of polymer-dependent interactions of human endothelial cells, smooth muscle cells, and platelets. Acta Biomater 2014; 10: 688-700.
• 195 Melchiorri AJ. et al. Strategies and techniques to enhance the in situ endothelialisation of small-diameter biodegradable polymeric vascular grafts. Tissue Eng Part B Rev 2013; 19: 292-307.
• 196 de Valence S. et al. Long term performance of polycaprolactone vascular grafts in a rat abdominal aorta replacement model. Biomaterials 2012; 33: 38-47.
• 197 Hynes RO. Cell-matrix adhesion in vascular development. J Thromb Haemost 2007; 5: 32-40.
• 198 Samples J. et al. Targeting angiogenesis and the tumor microenvironment. Surg Oncol Clin N Am 2013; 22: 629-639.
• 199 George EL. et al. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 1993; 119: 1079-1091.
• 200 Eming SA, Hubbell JA. Extracellular matrix in angiogenesis: dynamic structures with translational potential. Exp Dermatol 2011; 20: 605-613.
• 201 Seifert AW, Voss SR. Revisiting the relationship between regenerative ability and aging. BMC Biol 2013; 11: 2.
• 202 Calve S. et al. A transitional extracellular matrix instructs cell behavior during muscle regeneration. Dev Biol 2010; 344: 259-271.
• 203 Calve S, Simon HG. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration. FASEB J 2012; 26: 2538-2545.
• 204 Mercer SE. et al. A dynamic spatiotemporal extracellular matrix facilitates epi-cardial-mediated vertebrate heart regeneration. Dev Biol 2013; 382: 457-469.
• 205 Wang J. et al. Fibronectin is deposited by injury-activated epicardial cells and is necessary for zebrafish heart regeneration. Dev Biol 2013; 382: 427-435.
• 206 Weaver VM. et al. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol 1997; 137: 231-245.
• 207 Watt FM, Huck WT. Role of the extracellular matrix in regulating stem cell fate. Nat Rev Mol Cell Biol 2013; 14: 467-473.
• 208 Hofmann S. et al. Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds. Biomaterials 2007; 28: 1152-1162.
• 209 Badylak S. et al. Resorbable bioscaffold for esophageal repair in a dog model. J Pediatr Surg 2000; 35: 1097-1103.
• 210 Busch SA, Silver J. The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 2007; 17: 120-127.
• 211 Oka T. et al. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling. Circ Res 2007; 101: 313-321.
• 212 Lee B. et al. Perlecan domain V is neuroprotective and proangiogenic following ischaemic stroke in rodents. J Clin Invest 2011; 121: 3005-3023.
• 213 Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res 2014; 163: 268-285.
• 214 Faulk DM. et al. Role of the extracellular matrix in whole organ engineering. J Cell Physiol 2014; 229: 984-989.
• 215 Keane TJ, Badylak SF. The host response to allogeneic and xenogeneic biological scaffold materials. J Tissue Eng Regen Med. 2014 Epub ahead of print.
• 216 Moroni F, Mirabella T. Decellularised matrices for cardiovascular tissue engineering. Am J Stem Cells 2014; 3: 1-20.
• 217 Aupecle B. et al. Intermediate follow-up of a composite stentless porcine valved conduit of bovine pericardium in the pulmonary circulation. Ann Thorac Surg 2002; 74: 127-132.
• 218 Neethling WM. et al. Evaluation of a tissue-engineered bovine pericardial patch in paediatric patients with congenital cardiac anomalies: initial experience with the ADAPT-treated CardioCel(R) patch. Interact Cardiovasc Thorac Surg 2013; 17: 698-702.
• 219 Neumann A. et al. Early systemic cellular immune response in children and young adults receiving decellularised fresh allografts for pulmonary valve replacement. Tissue Eng Part A 2014; 20: 1003-1011.
• 220 Ott HC. et al. Perfusion-decellularised matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 2008; 14: 213-221.
• 221 Wainwright JM. et al. Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng Part C Methods 2010; 16: 525-532.
• 222 Aubin H. et al. Decellularised whole heart for bioartificial heart. Methods Mol Biol 2013; 1036: 163-178.
• 223 Shevach M. et al. Fabrication of omentum-based matrix for engineering vascularised cardiac tissues. Biofabrication 2014; 6: 024101.
• 224 Robertson MJ. et al. Optimising recellularisation of whole decellularised heart extracellular matrix. PloS One 2014; 9: e90406.
• 225 Lu TY. et al. Repopulation of decellularised mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun 2013; 4: 2307.
• 226 Yasui H. et al. Excitation propagation in three-dimensional engineered hearts using decellularised extracellular matrix. Biomaterials 2014; 35: 7839-7850.
• 227 Keane TJ. et al. Consequences of ineffective decellularisation of biologic scaffolds on the host response. Biomaterials 2012; 33: 1771-1781.
• 228 Macher BA, Galili U. The Galalpha1,3Galbeta1,4GlcNAc-R (alpha-Gal) epi-tope: a carbohydrate of unique evolution and clinical relevance. Biochim Biophys Acta 2008; 1780: 75-88.
• 229 Daly KA. et al. Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng Part A 2009; 15: 3877-3888.
• 230 Garkavenko O. et al. Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study. J Med Virol 2008; 80: 2046-2052.
• 231 Didangelos A. et al. Proteomics characterisation of extracellular space components in the human aorta. Mol Cell Proteomics 2010; 9: 2048-2062.
• 232 Xu J, Shi GP. Vascular wall extracellular matrix proteins and vascular diseases. Biochim Biophys Acta. 2014 Epub ahead of print.
• 233 Amento EP. et al. Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb. 1991; 11: 1223-1230.
• 234 Neve A. et al. Extracellular matrix modulates angiogenesis in physiological and pathological conditions. Biomed Res Int 2014; 2014: 756078.
• 235 Aszodi A. et al. What mouse mutants teach us about extracellular matrix function. Annu Rev Cell Dev Biol 2006; 22: 591-621.
• 236 Daley WP. et al. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci 2008; 121: 255-264.
• 237 Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009; 326: 1216-1219.
• 238 Bornstein P. et al. Synthesis and Secretion of Structural Macromolecules by endothelial Cells in Culture. In: Pathobiology of the Endothelial Cell. Elsevier Inc.; 1982. pp. 215-228.
• 239 Schwartz MA. Integrin signaling revisited. Trends Cell Biol 2001; 11: 466-470.
• 240 Hinek A. Biological roles of the non-integrin elastin/laminin receptor. Biol Chem 1996; 377: 471-480.
• 241 Moiseeva EP. Adhesion receptors of vascular smooth muscle cells and their functions. Cardiovasc Res 2001; 52: 372-386.
• 242 Ito S. et al. Inhibitory effect of type 1 collagen gel containing alpha-elastin on proliferation and migration of vascular smooth muscle and endothelial cells. Cardiovasc Surg 1997; 5: 176-183.
• 243 Li DY. et al. Elastin is an essential determinant of arterial morphogenesis. Nature 1998; 393: 276-280.
• 244 Vogel W. et al. The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1997; 1: 13-23.
• 245 Pozzi A. et al. Integrin alpha1beta1 mediates a unique collagen-dependent proliferation pathway in vivo. J Cell Biol 1998; 142: 587-594.
• 246 Kemeny SF. et al. Glycated collagen and altered glucose increase endothelial cell adhesion strength. J Cell Physiol 2013; 228: 1727-1736.
• 247 Naugle JE. et al. Type VI collagen induces cardiac myofibroblast differentiation: implications for postinfarction remodeling. Am J Physiol Heart Circ Physiol 2006; 290: H323-330.
• 248 Lee S. et al. Processing of VEGF-A by matrix metalloproteinases regulates bioa-vailability and vascular patterning in tumors. J Cell Biol 2005; 169: 681-691.
• 249 Pan Y. et al. Bud specific N-sulfation of heparan sulfate regulates Shp2-dependent FGF signaling during lacrimal gland induction. Development 2008; 135: 301-310.
• 250 Fuster MM. et al. Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis. J Cell Biol 2007; 177: 539-549.
• 251 Sugaya N. et al. 6-O-sulfation of heparan sulfate differentially regulates various fibroblast growth factor-dependent signalings in culture. J Biol Chem 2008; 283: 10366-10376.
• 252 Bellon G. et al. Matrix metalloproteinases and matrikines in angiogenesis. Crit Rev Oncol Hematol 2004; 49: 203-220.
• 253 Adair-Kirk TL, Senior RM. Fragments of extracellular matrix as mediators of inflammation. Int J Biochem Cell Biol 2008; 40: 1101-1110.
• 254 Mammoto A. et al. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 2009; 457: 1103-1108.
• 255 Gerstel D. et al. CEACAM1 creates a proangiogenic tumor microenvironment that supports tumor vessel maturation. Oncogene 2011; 30: 4275-4288.
• 256 Yang W, Yee AJ. Versican V2 isoform enhances angiogenesis by regulating endothelial cell activities and fibronectin expression. FEBS Lett 2013; 587: 185-192.
• 257 Kim BR. et al. Therapeutic angiogenesis in a murine model of limb ischaemia by recombinant periostin and its fasciclin I domain. Biochim Biophys Acta 2014; 1842: 1324-1332.
• 258 Ciucurel EC, Sefton MV. Del-1 overexpression in endothelial cells increases vascular density in tissue-engineered implants containing endothelial cells and adipose-derived mesenchymal stromal cells. Tissue Eng Part A 2014; 20: 1235-1252.
• 259 Mammadov R. et al. Heparin mimetic peptide nanofibers promote angiogenesis. Biomacromolecules 2011; 12: 3508-3519.
• 260 Grant DS. et al. Interaction of endothelial cells with a laminin A chain peptide (SIKVAV) in vitro and induction of angiogenic behavior in vivo. J Cell Physiol 1992; 153: 614-625.
• 261 Simon-Assmann P. et al. Role of laminins in physiological and pathological angiogenesis. Int J Dev Biol 2011; 55: 455-465.
• 262 Pati F. et al. Printing three-dimensional tissue analogues with decellularised extracellular matrix bioink. Nat Commun 2014; 5: 3935.
• 263 Patra C. et al. Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish. Development 2011; 138: 4499-4509.
• 264 Brandenberger R. et al. Identification and characterisation of a novel extracellular matrix protein nephronectin that is associated with integrin alpha8beta1 in the embryonic kidney. J Cell Biol 2001; 154: 447-458.
• 265 Patra C. et al. The functional properties of nephronectin: an adhesion molecule for cardiac tissue engineering. Biomaterials 2012; 33: 4327-4335.
• 266 Nikolic I. et al. EGFL7 ligates alphavbeta3 integrin to enhance vessel formation. Blood 2013; 121: 3041-3050.
• 267 Seol YJ. et al. Bioprinting technology and its applications. Eur J Cardiothorac Surg 2014; 46: 342-348.
• 268 Kolesky DB. et al. 3D bioprinting of vascularised, heterogeneous cell-laden tissue constructs. Adv Mater 2014; 26: 3124-3130.
• 269 Han LH. et al. Dynamic tissue engineering scaffolds with stimuli-responsive macroporosity formation. Biomaterials 2013; 34: 4251-4258