Models of immunogenicity in preclinical assessment of tissue engineered heart valves

Acta Biomaterialia - Tập 133 - Trang 102-113 - 2021
Marcus Ground1, Steve Waqanivavalagi2,3, Robert Walker1, Paget Milsom4, Jillian Cornish2
1Department of Medicine, University of Otago, Dunedin 9016, New Zealand
2Department of Medicine, University of Auckland, Grafton, Auckland 1024, New Zealand
3Adult Emergency Department, Auckland City Hospital, Auckland District Health Board, Grafton, Auckland, 1023, New Zealand
4Green Lane Cardiothoracic Surgical Unit, Auckland City Hospital, Auckland District Health Board, Grafton, Auckland, 1023, New Zealand

Tài liệu tham khảo

Yacoub, 2005, Will heart valve tissue engineering change the world?, Nat. Clin. Pract. Cardiovasc. Med., 2, 60, 10.1038/ncpcardio0112 Coffey, 2016, The modern epidemiology of heart valve disease, Heart, 102, 75, 10.1136/heartjnl-2014-307020 H. Baumgartner, V. Falk, J.J. Bax, M. De Bonis, C. Hamm, P.J. Holm, B. Iung, P. Lancellotti, E. Lansac, D.R. Muñoz, R. Rosenhek, J. Sjögren, P. Tornos Mas, A. Vahanian, T. Walther, O. Wendler, S. Windecker, J.L. Zamorano, M. Roffi, O. Alfieri, S. Agewall, A. Ahlsson, E. Barbato, H. Bueno, J.P. Collet, I.M. Coman, M. Czerny, V. Delgado, D. Fitzsimons, T. Folliguet, O. Gaemperli, G. Habib, W. Harringer, M. Haude, G. Hindricks, H.A. Katus, J. Knuuti, P. Kolh, C. Leclercq, T.A. McDonagh, M.F. Piepoli, L.A. Pierard, P. Ponikowski, G.M.C. Rosano, F. Ruschitzka, E. Shlyakhto, I.A. Simpson, M. Sousa-Uva, J. Stepinska, G. Tarantini, D. Tche, V. Aboyans, H.K. Kzhdryan, J. Mascherbauer, F. Samadov, V. Shumavets, G. Van Camp, D. Loncar, D. Lovric, G.M. Georgiou, K. Linhartova, N. Ihlemann, M. Abdelhamid, T. Pern, A. Turpeinen, E. Srbinovska-Kostovska, A. Cohen, Z. Bakhutashvili, H. Ince, M. Vavuranakis, A. Temesvari, T. Gudnason, D. Mylotte, R. Kuperstein, C. Indolfi, Y. Pya, G. Bajraktari, A. Kerimkulova, A. Rudzitis, V. Mizariene, F. Lebrun, D.C. Demarco, L. Oukerraj, B.J. Bouma, T.K. Steigen, M. Komar, L.M. De Moura Branco, B.A. Popescu, V. Uspenskiy, M. Foscoli, L. Jovovic, I. Simkova, M. Bunc, J.A.V. de Prada, M. Stagmo, B.A. Kaufmann, A. Mahdhaoui, E. Bozkurt, E. Nesukay, S.J.D. Brecker, 2017 ESC/EACTS Guidelines for the management of valvular heart disease, 2017. https://doi.org/10.1093/eurheartj/ehx391. Kostyunin, 2020, Degeneration of bioprosthetic heart valves: update 2020, J. Am. Heart Assoc., 9, 10.1161/JAHA.120.018506 Badylak, 2014, Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response, Ann. Biomed. Eng., 42, 1517, 10.1007/s10439-013-0963-7 Nachlas, 2017, Developing a clinically relevant tissue engineered heart valve—a review of current approaches, Adv. Healthc. Mater., 6, 1 Cheung, 2015, Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions, Expert Opin. Biol. Ther., 15, 1155, 10.1517/14712598.2015.1051527 Platt, 2002, Recommendations of the national heart, lung, and blood institute heart and lung xenotransplantation working group, Circulation, 106, 1043, 10.1161/01.CIR.0000031064.67525.28 Joseph, 2020, Setting standards: revised ISO 5840 series clarifies testing, evaluation procedures for cardiac valves, Biomed. Instrum. Technol., 54, 441, 10.2345/0899-8205-54.6.441 Zhang, 2019, Preclinical assessment of cardiac valve substitutes: current status and considerations for engineered tissue heart valves, Front. Cardiovasc. Med., 6, 1, 10.3389/fcvm.2019.00072 Crapo, 2011, An overview of tissue and whole organ decellularization processes, Biomaterials, 32, 3233, 10.1016/j.biomaterials.2011.01.057 Van Der Rest, 1991, Collagen family of proteins, FASEB J, 5, 2814, 10.1096/fasebj.5.13.1916105 Brown, 2014 Wong, 2014, Immunogenicity in xenogeneic scaffold generation: antigen removal vs. decellularization, Acta Biomater, 10, 1806, 10.1016/j.actbio.2014.01.028 Dalgliesh, 2018, Graft-specific immune tolerance is determined by residual antigenicity of xenogeneic extracellular matrix scaffolds, Acta Biomater, 79, 253, 10.1016/j.actbio.2018.08.016 Kasimir, 2005, Presence and elimination of the xenoantigen Gal (α1, 3) Gal in tissue-engineered heart valves, Tissue Eng, 11, 1274, 10.1089/ten.2005.11.1274 Galili, 1998 Tector, 2020, The possible role of Anti-Neu5Gc as an obstacle in xenotransplantation, Front. Immunol., 11, 1, 10.3389/fimmu.2020.00622 Burlak, 2014, Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs, Am. J. Transplant., 14, 1895, 10.1111/ajt.12744 Cravedi, 2017, Regenerative immunology: the immunological reaction to biomaterials, Transpl. Int., 30, 1199, 10.1111/tri.13068 Brown, 2012, Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials, Acta Biomater, 8, 978, 10.1016/j.actbio.2011.11.031 Land, 2015, The role of damage-associated molecular patterns (DAMPs) in human diseases part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine, Sultan Qaboos Univ. Med. J., 15, e157 van Loon, 2013, The immune response in in situ tissue engineering of aortic heart valves, 137 Simon, 2003, Early failure of the tissue engineered porcine heart valve SYNERGRAFTTM in pediatric patients, Eur. J. Cardio-Thoracic Surg., 23, 1002, 10.1016/S1010-7940(03)00094-0 Brown, 2011, Performance of SynerGraft decellularized pulmonary homograft in patients undergoing a Ross procedure, Ann. Thorac. Surg., 91, 416, 10.1016/j.athoracsur.2010.10.069 Erdbrügger, 2006, Decellularized xenogenic heart valves reveal remodeling and growth potential in vivo, Tissue Eng, 12, 2059, 10.1089/ten.2006.12.2059 Weymann, 2010, Clinical experience with expanded use of the ross procedure: a paradigm shift?, J. Heart Valve Dis., 19, 279 Rüffer, 2010, Early failure of xenogenous de-cellularised pulmonary valve conduits - a word of caution!, Eur. J. Cardio-Thoracic Surg., 38, 78, 10.1016/j.ejcts.2010.01.044 Christ, 2019, Long-term results after the ross procedure with the decellularized autotissue matrix P® bioprosthesis used for pulmonary valve replacement, Eur. J. Cardio-Thoracic Surg., 55, 885, 10.1093/ejcts/ezy377 Zhang, 2015, Application of hydrogels in heart valve tissue engineering, J. Long. Term. Eff. Med. Implants., 25, 105, 10.1615/JLongTermEffMedImplants.2015011817 Anderson, 2008, Foreign body reaction to biomaterials, Semin. Immunol., 20, 86, 10.1016/j.smim.2007.11.004 Wong, 2016, In vivo xenogeneic scaffold fate is determined by residual antigenicity and extracellular matrix preservation, Biomaterials, 92, 1, 10.1016/j.biomaterials.2016.03.024 Rutkovskiy, 2017, Valve interstitial cells: the key to understanding the pathophysiology of heart valve calcification, J. Am. Heart Assoc., 6, 10.1161/JAHA.117.006339 Costa-Pinto, 2016, Testing natural biomaterials in animal models, Biomater. from Nat. Adv. Devices Ther., 562, 10.1002/9781119126218.ch30 Aamodt, 2016, Extracellular matrix-based biomaterial scaffolds and the host response, Biomaterials, 86, 68, 10.1016/j.biomaterials.2016.02.003 Daly, 2009, Effect of the αgal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model, Tissue Eng. - Part A., 15, 3877, 10.1089/ten.tea.2009.0089 Charles A Janeway, 2001 Alvarez, 2016, Delivery strategies to control inflammatory response: modulating M1–M2 polarization in tissue engineering applications, J. Control. Release., 240, 349, 10.1016/j.jconrel.2016.01.026 Martinez, 2014, The M1 and M2 paradigm of macrophage activation: time for reassessment, F1000Prime Rep., 6, 1, 10.12703/P6-13 Wissing, 2019, Macrophage-driven biomaterial degradation depends on scaffold microarchitecture, Front. Bioeng. Biotechnol., 7, 10.3389/fbioe.2019.00087 Fenwick, 2009, The welfare of animals used in science: how the “Three Rs” ethic guides improvements, Can. Vet. J. = La Rev. Vet. Can., 50, 523 Blum, 2018, Tissue-engineered heart valves: a call for mechanistic studies, Tissue Eng. - Part B Rev., 24, 240, 10.1089/ten.teb.2017.0425 Helder, 2017, Xenoantigenicity of porcine decellularized valves, J. Cardiothorac. Surg., 12, 1, 10.1186/s13019-017-0621-5 Liu, 2018, Comparison of detergent-based decellularization protocols for the removal of antigenic cellular components in porcine aortic valve, Xenotransplantation, 25, e12380, 10.1111/xen.12380 Methe, 2014, An alternative approach to decellularize whole porcine heart, Biores. Open Access., 3, 327, 10.1089/biores.2014.0046 Sierad, 2015, Functional heart valve scaffolds obtained by complete Decellularization of porcine aortic roots in a novel differential pressure gradient perfusion system, Tissue Eng. Part C. Methods., 21, 1284, 10.1089/ten.tec.2015.0170 Guo, 2018, Radical polymerization-crosslinking method for improving extracellular matrix stability in bioprosthetic heart valves with reduced potential for calcification and inflammatory response, Acta Biomater, 82, 44, 10.1016/j.actbio.2018.10.017 Lichtenberg, 2006, In vitro re-endothelialization of detergent decellularized heart valves under simulated physiological dynamic conditions, Biomaterials, 27, 4221, 10.1016/j.biomaterials.2006.03.047 Costa, 2012, Cryopreservation of cell/scaffold tissue-engineered constructs, Tissue Eng. Part C. Methods., 18, 852, 10.1089/ten.tec.2011.0649 Merna, 2013, Optical imaging predicts mechanical properties during decellularization of cardiac tissue, Tissue Eng. Part C. Methods., 19, 802, 10.1089/ten.tec.2012.0720 Xing, 2015, Decellularization of fibroblast cell sheets for natural extracellular matrix scaffold preparation, Tissue Eng. Part C. Methods., 21, 77, 10.1089/ten.tec.2013.0666 Scientific, 2016, Thermo scientific NanoDrop one user guide, Thermo Sci. NanoDrop One User Guid. Revision B, 18 Lee, 2014, Advances in forensic DNA quantification: a review, Electrophoresis, 35, 3044, 10.1002/elps.201400187 ThermoFisher, Quant-it PicoGreen dsDNA Reagent and Kits, (2008) 1–7. https://www.thermofisher.com/document-connect/document-connect.html?url=https%3A%2F%2Fassets.thermofisher.com%2FTFS-Assets%2FLSG%2Fmanuals%2Fmp07581.pdf&title=UXVhbnQtaVQgUGljb0dyZWVuIGRzRE5BIFJlYWdlbnQgYW5kIEtpdHM=. Gilbert, 2009, Quantification of DNA in biologic scaffold materials, J. Surg. Res., 152, 135, 10.1016/j.jss.2008.02.013 B.D. Ratner, A.S. Hoffman, F.J. Schoen, J.E. Lemons, An Introduction to Materials in Medicine, 2004. Kluin, 2017, In situ heart valve tissue engineering using a bioresorbable elastomeric implant – From material design to 12 months follow-up in sheep, Biomaterials, 125, 101, 10.1016/j.biomaterials.2017.02.007 Gong, 2020, A resazurin-based, nondestructive assay for monitoring cell proliferation during a scaffold-based 3D culture process, Regen. Biomater., 7, 271, 10.1093/rb/rbaa002 Khorramirouz, 2019, In Vivo response of acellular porcine pericardial for tissue engineered transcatheter aortic valves, Sci. Rep., 9, 1, 10.1038/s41598-018-37550-2 Dai, 2019, Modifying decellularized aortic valve scaffolds with stromal cell-derived factor-1α loaded proteolytically degradable hydrogel for recellularization and remodeling, Acta Biomater, 88, 280, 10.1016/j.actbio.2019.02.002 Murray, 2017, Macrophage Polarization, Annu. Rev. Physiol., 79, 541, 10.1146/annurev-physiol-022516-034339 VeDepo, 2018, Extended bioreactor conditioning of mononuclear cell–seeded heart valve scaffolds, J. Tissue Eng., 9, 10.1177/2041731418767216 Orecchioni, 2019, Macrophage Polarization : different Gene Signatures in M1 (LPS +) vs . Classically and M2 (LPS –) vs, Alternativel. Activat. Macrophages,, 10, 1 Cesarovic, 2020, Animals in cardiovascular research, Eur. Heart J., 41, 200, 10.1093/eurheartj/ehz933 Ribitsch, 2020, Large animal models in regenerative medicine and tissue engineering: To Do or Not to Do, Front. Bioeng. Biotechnol., 8, 1, 10.3389/fbioe.2020.00972 Mestas, 2004, Of mice and not men: differences between mouse and human immunology, J. Immunol., 172, 2731, 10.4049/jimmunol.172.5.2731 Bailey, 2013, The evolutionary basis for differences between the immune systems of man, mouse, pig and ruminants, Vet. Immunol. Immunopathol., 152, 13, 10.1016/j.vetimm.2012.09.022 Rashid, 2004, The use of animal models in developing the discipline of cardiovascular tissue engineering: a review, Biomaterials, 25, 1627, 10.1016/S0142-9612(03)00522-2 Tardif, 2013, IACUC Review of nonhuman primate research, ILAR J, 54, 234, 10.1093/ilar/ilt040 Tillman, 1981, Platelet function and coagulation parameters in sheep during experimental vascular surgery, Lab. Anim. Sci., 31, 263 Weber, 2013, Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model, Biomaterials, 34, 7269, 10.1016/j.biomaterials.2013.04.059 Dekker, 2018, Sheep-specific immunohistochemical panel for the evaluation of regenerative and inflammatory processes in tissue-engineered heart valves, Front. Cardiovasc. Med., 5, 1, 10.3389/fcvm.2018.00105 Gallo, 2017, The Vietnamese pig as a translational animal model to evaluate tissue engineered heart valves: promising early experience, Int. J. Artif. Organs., 40, 142, 10.5301/ijao.5000568 Rehli, 2002, Of mice and men: species variations of Toll-like receptor expression, Trends Immunol, 23, 375, 10.1016/S1471-4906(02)02259-7 Del Prete, 1993, Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production, J. Immunol., 150, 353, 10.4049/jimmunol.150.2.353 Pabst, 2020, The pig as a model for immunology research, Cell Tissue Res, 380, 287, 10.1007/s00441-020-03206-9 Scheerlinck, 2016 Dawson, 2017, An in-depth comparison of the porcine, murine and human inflammasomes; lessons from the porcine genome and transcriptome, Vet. Microbiol., 202, 2, 10.1016/j.vetmic.2016.05.013 Messaoudi, 2011, Nonhuman primate models of human immunology, Antioxidants Redox Signal, 14, 261, 10.1089/ars.2010.3241 Galili, 1988, Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells, J. Biol. Chem., 263, 17755, 10.1016/S0021-9258(19)77900-9 Steinke, 2015, The alpha-gal story: lessons learned from connecting the dots, J. Allergy Clin. Immunol., 135, 589, 10.1016/j.jaci.2014.12.1947 Padler-Karavani, 2011, Potential impact of the non-human sialic acid N-glycolylneuraminic acid on transplant rejection risk, Xenotransplantation, 18, 1, 10.1111/j.1399-3089.2011.00622.x LaTemple, 1998, Adult and neonatal anti-Gal response in knock-out mice for α1,3 galactosyltransferase, Xenotransplantation, 5, 191, 10.1111/j.1399-3089.1998.tb00027.x Kim, 2015, Differences in xenoreactive immune response and patterns of calcification of porcine and bovine tissues in α-Gal knock-out and wild-type mouse implantation models, Eur. J. Cardio-Thoracic Surg., 48, 392, 10.1093/ejcts/ezu501 Tahara, 2010, Immunological property of antibodies against N -Glycolylneuraminic acid epitopes in cytidine Monophospho– N -Acetylneuraminic acid hydroxylase-deficient mice, J. Immunol., 184, 3269, 10.4049/jimmunol.0902857 Galili, 2013, Galactosyltransferase knockout pigs produce the natural anti-Gal antibody and simulate the evolutionary appearance of this antibody in primates, Xenotransplantation, 20, 267, 10.1111/xen.12051 Wells, 2010, Genetically modified animals and pharmacological research, 213 Wang, 2014, Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non-human primates, Xenotransplantation, 21, 376, 10.1111/xen.12106 Wang, 2019, Antigenicity of tissues and organs from GGTA1/CMAH/β4GalNT2 triple gene knockout pigs, J. Biomed. Res., 33, 235, 10.7555/JBR.32.20180018 Lee, 2016, Initial in vitro studies on tissues and cells from GTKO/CD46/NeuGcKO pigs, Xenotransplantation, 23, 137, 10.1111/xen.12229 Reimer, 2017, Implantation of a tissue-engineered tubular heart valve in growing lambs, Ann. Biomed. Eng., 45, 439, 10.1007/s10439-016-1605-7 Kheradvar, 2017, Animal models for heart valve research and development, Drug Discov. Today Dis. Model., 24, 55, 10.1016/j.ddmod.2018.04.001 Weber, 2011, Tissue engineering on matrix: future of autologous tissue replacement, Semin. Immunopathol., 33, 307, 10.1007/s00281-011-0258-8 James, 2015, Hemodynamic characterization of a mouse model for investigating the cellular and molecular mechanisms of neotissue formation in tissue-engineered heart valves, Tissue Eng. Part C Methods., 21, 987, 10.1089/ten.tec.2015.0011 Jana, 2019, Trilayered tissue structure with leaflet-like orientations developed through in vivo tissue engineering, Biomed. Mater., 15, 10.1088/1748-605X/ab52e2 Syedain, 2015, 6-Month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep, Biomaterials, 73, 175, 10.1016/j.biomaterials.2015.09.016 Lattouf, 2014, Picrosirius red staining, J. Histochem. Cytochem., 62, 751, 10.1369/0022155414545787 Emmert, 2018, Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model, Sci. Transl. Med., 10, 10.1126/scitranslmed.aan4587 Bennink, 2018, A novel restorative pulmonary valved conduit in a chronic sheep model: mid-term hemodynamic function and histologic assessment, J. Thorac. Cardiovasc. Surg., 155, 2591, 10.1016/j.jtcvs.2017.12.046 Fioretta, 2020, Differential leaflet remodeling of bone marrow cell pre-seeded versus nonseeded bioresorbable transcatheter pulmonary valve replacements, JACC Basic to Transl. Sci., 5, 15, 10.1016/j.jacbts.2019.09.008 van Rijswijk, 2020, Failure of decellularized porcine small intestinal submucosa as a heart valved conduit, J. Thorac. Cardiovasc. Surg., 160, e201, 10.1016/j.jtcvs.2019.09.164 Meyerholz, 2018, Fundamental concepts for semiquantitative tissue scoring in translational research, ILAR J, 59, 13, 10.1093/ilar/ily025 Khorramirouz, 2018, A novel surgical technique for a rat subcutaneous implantation of a tissue engineered scaffold, Acta Histochem, 120, 282, 10.1016/j.acthis.2018.02.010 Theodoridis, 2015, Successful matrix guided tissue regeneration of decellularized pulmonary heart valve allografts in elderly sheep, Biomaterials, 52, 221, 10.1016/j.biomaterials.2015.02.023 Zafar, 2015, Physiological growth, remodeling potential, and preserved function of a novel bioprosthetic tricuspid valve: tubular bioprosthesis made of small intestinal submucosa-derived extracellular matrix, J. Am. Coll. Cardiol., 66, 877, 10.1016/j.jacc.2015.06.1091 Weber, 2011, Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates, Eur. Heart J., 32, 2830, 10.1093/eurheartj/ehr059 Motta, 2020, Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo, Sci. Rep., 10, 1, 10.1038/s41598-020-76322-9 Driessen-Mol, 2014, Transcatheter implantation of homologous “Off-the-Shelf” tissue-engineered heart valves with self-repair capacity, J. Am. Coll. Cardiol., 63, 1320, 10.1016/j.jacc.2013.09.082 Fallon, 2014, In vivo remodeling potential of a novel bioprosthetic tricuspid valve in an ovine model, J. Thorac. Cardiovasc. Surg., 148, 333, 10.1016/j.jtcvs.2013.10.048 Karrouf, 2016, Prosthetics and techniques in repair of Animal's Abdominal wall, Scientifica (Cairo), 2016 Lim, 2013, In Vivo efficacy of alpha-galactosidase as possible promise for prolonged durability of bioprosthetic heart valve using alpha1,3-galactosyltransferase knockout mouse, Tissue Eng. - Part A., 19, 2339, 10.1089/ten.tea.2013.0062 Tao, 2017, Making mouse models that reflect human immune responses, Trends Immunol, 38, 181, 10.1016/j.it.2016.12.007 Lintas, 2018, Development of a novel human cell-derived tissue-engineered heart valve for transcatheter aortic valve replacement: an in vitro and in vivo feasibility study, J. Cardiovasc. Transl. Res., 11, 470, 10.1007/s12265-018-9821-1 Driessen-Mol, 2014, Transcatheter implantation of homologous “off-the-shelf” tissue-engineered heart valves with self-repair capacity: long-term functionality and rapid in vivo remodeling in sheep, J. Am. Coll. Cardiol., 63, 1320, 10.1016/j.jacc.2013.09.082 Emmert, 2012, Stem cell-based transcatheter aortic valve implantation: first experiences in a pre-clinical model, JACC Cardiovasc. Interv., 5, 874, 10.1016/j.jcin.2012.04.010 Theodoridis, 2017, Six-Year-old sheep as a clinically relevant large animal model for aortic valve replacement using tissue-engineered grafts based on decellularized allogenic matrix, Tissue Eng. - Part C Methods., 23, 953, 10.1089/ten.tec.2017.0163 Coyan, 2020, Acute In Vivo functional assessment of a biodegradable stentless elastomeric tricuspid valve, J. Cardiovasc. Transl. Res., 13, 796, 10.1007/s12265-020-09960-z Meurens, 2012, The pig: a model for human infectious diseases, Trends Microbiol, 20, 50, 10.1016/j.tim.2011.11.002 Kuwaki, 2005, Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience, Nat. Med., 11, 29, 10.1038/nm1171 Yamada, 2005, Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue, Nat. Med., 11, 32, 10.1038/nm1172 Fang, 2012, Anti-gal antibodies in α1,3-galactosyltransferase gene-knockout pigs, Xenotransplantation, 19, 305, 10.1111/j.1399-3089.2012.00710.x Yamamoto, 2020, Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout), Sci. Rep., 10, 1, 10.1038/s41598-020-66311-3 Waqanivavalagi, 2020, Clinical performance of decellularized heart valves versus standard tissue conduits: a systematic review and meta-analysis, Journal of Cardiothoracic Surgery, 10.1186/s13019-020-01292-y