{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:35:45Z","timestamp":1792636545561,"version":"4.5.0"},"reference-count":170,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Social Fund","award":["ESF \/14-BM-A55-0028\/18"],"award-info":[{"award-number":["ESF \/14-BM-A55-0028\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiovascular diseases represent a major health concern worldwide with few therapy options for ischemic injuries due to the limited regeneration potential of affected cardiomyocytes. Innovative cell replacement approaches could facilitate efficient regenerative therapy. However, despite extensive attempts to expand primary human cells in vitro, present technological limitations and the lack of human donors have so far prevented their broad clinical use. Cell xenotransplantation might provide an ethically acceptable unlimited source for cell replacement therapies and bridge the gap between waiting recipients and available donors. Pigs are considered the most suitable candidates as a source for xenogeneic cells and tissues due to their anatomical and physiological similarities with humans. The potential of porcine cells in the field of stem cell-based therapy and regenerative medicine is under intensive investigation. This review outlines the current progress and highlights the most promising approaches in xenogeneic cell therapy with a focus on the cardiovascular system.<\/jats:p>","DOI":"10.3390\/ijms21249686","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:42:09Z","timestamp":1608291729000},"page":"9686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7968-3152","authenticated-orcid":false,"given":"Anne-Marie","family":"Galow","sequence":"first","affiliation":[{"name":"Institute of Genome Biology, Leibniz Institute for Farm Animal Biology, 18196 Dummerstorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1215-5504","authenticated-orcid":false,"given":"Tom","family":"Goldammer","sequence":"additional","affiliation":[{"name":"Institute of Genome Biology, Leibniz Institute for Farm Animal Biology, 18196 Dummerstorf, Germany"},{"name":"Molecular Biology and Fish Genetics Unit, Faculty of Agriculture and Environmental Sciences, University of Rostock, 18059 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2018-2836","authenticated-orcid":false,"given":"Andreas","family":"Hoeflich","sequence":"additional","affiliation":[{"name":"Institute of Genome Biology, Leibniz Institute for Farm Animal Biology, 18196 Dummerstorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1755-1536-5-19","article-title":"Common threads in cardiac fibrosis, infarct scar formation, and wound healing","volume":"5","author":"Czubryt","year":"2012","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1056\/NEJMoa060186","article-title":"Intracoronary bone marrow\u2013derived progenitor cells in acute myocardial infarction","volume":"355","author":"Erbs","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.amjcard.2004.03.034","article-title":"Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction","volume":"94","author":"Chen","year":"2004","journal-title":"Am. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0140-6736(12)60195-0","article-title":"Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): A prospective, randomised phase 1 trial","volume":"379","author":"Makkar","year":"2012","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1161\/CIRCULATIONAHA.112.092627","article-title":"Administration of cardiac stem cells in patients with ischemic cardiomyopathy (the SCIPIO Trial): Surgical aspects and interim analysis of myocardial function and viability by magnetic resonance","volume":"126","author":"Chugh","year":"2012","journal-title":"Circulation"},{"key":"ref_6","unstructured":"Malik, N. (2012). Allogeneic Versus Autologous Stem-Cell Therapy, BioPharm International."},{"key":"ref_7","first-page":"7","article-title":"A comparative anatomic and physiologic overview of the porcine heart","volume":"53","author":"Lelovas","year":"2014","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"858","DOI":"10.2337\/diab.40.7.858","article-title":"Persistent reversal of diabetes by transplantation of fetal pig proislets into nude mice","volume":"40","author":"Liu","year":"1991","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1097\/00007890-199312000-00013","article-title":"A diabetic rabbit model for pig islet xenotransplantation","volume":"56","author":"Tze","year":"1993","journal-title":"Transplantation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/S0140-6736(94)90570-3","article-title":"Transplantation of porcine fetal pancreas to diabetic patients","volume":"344","author":"Groth","year":"1994","journal-title":"Lancet Lond. Engl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJM199504273321702","article-title":"Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson\u2019s disease","volume":"332","author":"Kordower","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/nm1195-1189","article-title":"Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres","volume":"1","author":"Isacson","year":"1995","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1530\/eje.1.01982","article-title":"Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: A 4-year study","volume":"153","author":"Dorantes","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_14","first-page":"1134","article-title":"A clinical trial of xenotransplantation of neonatal pig islets for diabetic patients","volume":"36","author":"Wang","year":"2011","journal-title":"J. Cent. South Univ. Med Ed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1365-2249.2010.04273.x","article-title":"Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets","volume":"162","author":"White","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1631\/jzus.B1400310","article-title":"Treatment of diabetes with encapsulated pig islets: An update on current developments","volume":"16","author":"Zhu","year":"2015","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Galili, U., and Avila, J.L. (1999). Evolution of \u03b11,3Galactosyltransferase and of the \u03b1-Gal Epitope. \u03b1-Gal and Anti-Gal: \u03b11,3-Galactosyltransferase, \u03b1-Gal Epitopes, and the Natural Anti-Gal Antibody Subcellular Biochemistry, Springer. Subcellular Biochemistry.","DOI":"10.1007\/978-1-4615-4771-6_1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/0167-5699(93)90261-I","article-title":"Interaction of the natural anti-Gal antibody with \u03b1-galactosyl epitopes: A major obstacle for xenotransplantation in humans","volume":"14","author":"Galili","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_19","first-page":"411","article-title":"Hyperacute rejection in a discordant (pig to baboon) cardiac xenograft model","volume":"5","author":"Lexer","year":"1986","journal-title":"J. Heart Transpl."},{"key":"ref_20","first-page":"229","article-title":"Anti-Gal, alpha-Gal epitopes, and xenotransplantation","volume":"32","author":"Kobayashi","year":"1999","journal-title":"Subcell. Biochem."},{"key":"ref_21","first-page":"4543","article-title":"Experiences with known ABO-mismatched renal transplants","volume":"19","author":"Bannett","year":"1987","journal-title":"Transpl. Proc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1097\/00007890-199611270-00001","article-title":"In vivo immunoadsorption of antipig antibodies in baboons using a specific Gal(alpha)1-3Gal column","volume":"62","author":"Taniguchi","year":"1996","journal-title":"Transplantation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1399-3089.2004.00155.x","article-title":"Thrombotic microangiopathy and graft arteriopathy in pig hearts following transplantation into baboons","volume":"11","author":"Houser","year":"2004","journal-title":"Xenotransplantation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1097\/00007890-200011150-00010","article-title":"Coagulation and thrombotic disorders associated with pig organ and hematopoietic cell transplantation in nonhuman primates","volume":"70","author":"Basker","year":"2000","journal-title":"Transplantation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.4049\/jimmunol.155.11.5249","article-title":"Human anti-porcine xenogeneic T cell response. Evidence for allelic specificity of mixed leukocyte reaction and for both direct and indirect pathways of recognition","volume":"155","author":"Yamada","year":"1995","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/1074-7613(94)90009-4","article-title":"Porcine aortic endothelial cells activate human T cells: Direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28","volume":"1","author":"Murray","year":"1994","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1002\/eji.1830260630","article-title":"Detection of primary direct and indirect human anti-porcine T cell responses using a porcine dendritic cell population","volume":"26","author":"Dorling","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8789","DOI":"10.1073\/pnas.94.16.8789","article-title":"CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in\u2009primates","volume":"94","author":"Kirk","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/xen.12167","article-title":"Pig-to-baboon heterotopic heart transplantation--exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens","volume":"22","author":"Iwase","year":"2015","journal-title":"Xenotransplantation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1084\/jem.178.5.1801","article-title":"Long-term acceptance of major histocompatibility complex mismatched cardiac allografts induced by CTLA4Ig plus donor-specific transfusion","volume":"178","author":"Lin","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1399-3089.2004.00148.x","article-title":"Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation","volume":"11","author":"Knosalla","year":"2004","journal-title":"Xenotransplantation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1097\/00007890-199806150-00002","article-title":"Prolonged acceptance of concordant and discordant xenografts with combined CD40 and C28 pathway blockade","volume":"65","author":"Elwood","year":"1998","journal-title":"Transplantation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0966-3274(01)00040-5","article-title":"Blockade of the CD28 and CD40 pathways result in the acceptance of pig and rat islet xenografts but not rat cardiac grafts in mice","volume":"9","author":"Lehnert","year":"2001","journal-title":"Transpl. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1399-3089.2005.00221.x","article-title":"Co-stimulation blockade targeting CD154 and CD28\/B7 modulates the induced antibody response after a pig-to-baboon cardiac xenograft","volume":"12","author":"Wu","year":"2005","journal-title":"Xenotransplantation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/00007890-199109000-00029","article-title":"Inhibition of complement-mediated endothelial cell cytotoxicity by decay-accelerating factor. Potential for prevention of xenograft hyperacute rejection","volume":"52","author":"Dalmasso","year":"1991","journal-title":"Transplantation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1046\/j.0908-665X.2000.00085.x","article-title":"Human membrane cofactor protein (MCP, CD 46) protects transgenic pig hearts from hyperacute rejection in primates","volume":"8","author":"Adams","year":"2001","journal-title":"Xenotransplantation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1126\/science.1078942","article-title":"Production of alpha 1,3-galactosyltransferase-deficient pigs","volume":"299","author":"Phelps","year":"2003","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7335","DOI":"10.1073\/pnas.0307819101","article-title":"Production of -1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations","volume":"101","author":"Lai","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nm1171","article-title":"Heart transplantation in baboons using \u03b11,3-galactosyltransferase gene-knockout pigs as donors: Initial experience","volume":"11","author":"Kuwaki","year":"2005","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/TP.0b013e318199c34f","article-title":"The innate immune response and activation of coagulation in \u03b11,3-galactosyltransferase gene-knockout xenograft recipients","volume":"87","author":"Ezzelarab","year":"2009","journal-title":"Transplantation"},{"key":"ref_41","first-page":"1163","article-title":"In vitro investigation of pig cells for resistance to human antibody-mediated rejection","volume":"21","author":"Hara","year":"2008","journal-title":"Transpl. Int. Off. J. Eur. Soc. Organ Transpl."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1097\/TP.0b013e3182472850","article-title":"Human CD55 expression blocks hyperacute rejection and restricts complement activation in gal knockout cardiac xenografts","volume":"93","author":"McGregor","year":"2012","journal-title":"Transplantation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-3089.2011.00622.x","article-title":"Potential impact of the non-human sialic acid n-glycolylneuraminic acid on transplant rejection risk","volume":"18","author":"Varki","year":"2011","journal-title":"Xenotransplantation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/xen.12019","article-title":"Double knockout pigs deficient in N-glycolylneuraminic acid and galactose \u03b1-1,3-galactose reduce the humoral barrier to xenotransplantation","volume":"20","author":"Lutz","year":"2013","journal-title":"Xenotransplantation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/xen.12161","article-title":"Evaluation of human and nonhuman primate antibody binding to pig cells lacking GGTA1\/CMAH\/\u03b24GalNT2 genes","volume":"22","author":"Estrada","year":"2015","journal-title":"Xenotransplantation"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Phelps, C.J., Ball, S.F., Vaught, T.D., Vance, A.M., Mendicino, M., Monahan, J.A., Walters, A.H., Wells, K.D., Dandro, A.S., and Ramsoondar, J.J. (2009). Production and characterization of transgenic pigs expressing porcine CTLA4-Ig. Xenotransplantation.","DOI":"10.1111\/j.1399-3089.2009.00533.x"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/imm.12107","article-title":"Human dominant-negative class II transactivator transgenic pigs \u2013 effect on the human anti-pig T-cell immune response and immune status","volume":"140","author":"Hara","year":"2013","journal-title":"Immunology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1097\/TP.0b013e31819c85e8","article-title":"Suppression of human T-cell activation and expansion of regulatory T cells by pig cells overexpressing PD-ligands","volume":"87","author":"Plege","year":"2009","journal-title":"Transplantation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1189\/jlb.1210691","article-title":"Human PD-L1-overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells","volume":"90","author":"Ding","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1097\/TP.0b013e318188acb0","article-title":"Suppresive efficacy and proliferative capacity of human regulatory t cells in allogeneic and xenogeneic responses","volume":"86","author":"Lin","year":"2008","journal-title":"Transplantation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12015-013-9478-8","article-title":"The potential role of genetically-modified pig mesenchymal stromal cells in xenotransplantation","volume":"10","author":"Li","year":"2014","journal-title":"Stem Cell Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.jtcvs.2014.06.002","article-title":"Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation","volume":"148","author":"Mohiuddin","year":"2014","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1111\/j.1538-7836.2010.03950.x","article-title":"Atorvastatin or transgenic expression of tfpi inhibits coagulation initiated by anti-nongal igg binding to porcine aortic endothelial cells","volume":"8","author":"Lin","year":"2010","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1097\/TP.0000000000002443","article-title":"Perspectives on the optimal genetically-engineered pig in 2018 for initial clinical trials of kidney or heart xenotransplantation","volume":"102","author":"Cooper","year":"2018","journal-title":"Transplantation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-018-0765-z","article-title":"Consistent success in life-supporting porcine cardiac xenotransplantation","volume":"564","author":"Mayr","year":"2018","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.healun.2020.05.004","article-title":"Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation?","volume":"39","author":"Reichart","year":"2020","journal-title":"J. Heart Lung Transpl."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nm0298-141","article-title":"Uncertainty in xenotransplantation: Individual benefit versus collective risk","volume":"4","author":"Bach","year":"1998","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/34772","article-title":"Transgenic pigs and virus adaptation","volume":"391","author":"Weiss","year":"1998","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12595","DOI":"10.1111\/xen.12595","article-title":"Prevention of infection in xenotransplantation: Designated pathogen-free swine in the safety equation","volume":"27","author":"Fishman","year":"2020","journal-title":"Xenotransplantation"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Denner, J. (2020). Sensitive detection systems for infectious agents in xenotransplantation. Xenotransplantation, e12594.","DOI":"10.1111\/xen.12594"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/rmv.482","article-title":"Phylogenetic analysis of global hepatitis E virus sequences: Genetic diversity, subtypes and zoonosis","volume":"16","author":"Lu","year":"2006","journal-title":"Rev. Med. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/xen.12156","article-title":"Xenotransplantation and hepatitis E virus","volume":"22","author":"Denner","year":"2015","journal-title":"Xenotransplantation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3947\/ic.2013.45.3.260","article-title":"Cytomegalovirus infections in solid organ transplantation: A review","volume":"45","author":"Ramanan","year":"2013","journal-title":"Infect. Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Denner, J., L\u00e4ngin, M., Reichart, B., Kr\u00fcger, L., Fiebig, U., Mokelke, M., Radan, J., Mayr, T., Milusev, A., and Luther, F. (2020). Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival. bioRxiv.","DOI":"10.1101\/2020.04.07.029702"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger, L., L\u00e4ngin, M., Reichart, B., Fiebig, U., Kristiansen, Y., Prinz, C., Kessler, B., Egerer, S., Wolf, E., and Abicht, J.-M. (2019). Transmission of porcine circovirus 3 (PCV3) by xenotransplantation of pig hearts into baboons. Viruses, 11.","DOI":"10.3390\/v11070650"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Denner, J. (2016). How active are porcine endogenous retroviruses (PERVs)?. Viruses, 8.","DOI":"10.3390\/v8080215"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1128\/JVI.72.12.9986-9991.1998","article-title":"Host range and interference studies of three classes of pig endogenous retrovirus","volume":"72","author":"Takeuchi","year":"1998","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/39489","article-title":"Two sets of human-tropic pig retrovirus","volume":"389","author":"Stoye","year":"1997","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1034\/j.1399-3089.2000.00052.x","article-title":"Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV)","volume":"7","author":"Martin","year":"2000","journal-title":"Xenotransplantation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1126\/science.aad1191","article-title":"Genome-wide inactivation of porcine endogenous retroviruses (PERVs)","volume":"350","author":"Yang","year":"2015","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1126\/science.aan4187","article-title":"Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9","volume":"357","author":"Niu","year":"2017","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0065-230X(08)00005-5","article-title":"The tumorigenicity of human embryonic stem cells","volume":"100","author":"Blum","year":"2008","journal-title":"Adv. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0092-8674(03)00687-1","article-title":"Adult cardiac stem cells are multipotent and support myocardial regeneration","volume":"114","author":"Beltrami","year":"2003","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/CIRCRESAHA.108.178525","article-title":"Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function","volume":"103","author":"Marcello","year":"2008","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/35070587","article-title":"Bone marrow cells regenerate infarcted myocardium","volume":"410","author":"Orlic","year":"2001","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17783","DOI":"10.1073\/pnas.0706406104","article-title":"Bone marrow cells adopt the cardiomyogenic fate in vivo","volume":"104","author":"Rota","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","first-page":"e30","article-title":"Functional cardiomyocytes derived from human induced pluripotent stem cells","volume":"104","author":"Jianhua","year":"2009","journal-title":"Circ. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1161\/CIRCRESAHA.117.311504","article-title":"CCND2 overexpression enhances the regenerative potency of human induced pluripotent stem cell\u2013derived cardiomyocytes: remuscularization of injured ventricle","volume":"122","author":"Zhu","year":"2018","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jtcvs.2009.02.018","article-title":"Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart","volume":"138","author":"Hoashi","year":"2009","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_80","first-page":"14","article-title":"Myoblast transplantation for cardiac repair: A clinical perspective","volume":"9","author":"Haider","year":"2004","journal-title":"Mol. J. Am. Soc. Gene"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1161\/01.RES.0000155333.69009.63","article-title":"Clinical applications of stem cells for the heart","volume":"96","author":"Wollert","year":"2005","journal-title":"Circ. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ebiom.2017.01.029","article-title":"Stem cell technology in cardiac regeneration: A pluripotent stem cell promise","volume":"16","author":"Duelen","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.biopha.2018.10.065","article-title":"Stem cells as therapy for heart disease: IPSCs, ESCs, CSCs, and skeletal myoblasts","volume":"109","author":"Rikhtegar","year":"2019","journal-title":"Biomed. Pharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1161\/CIRCULATIONAHA.105.595181","article-title":"Life and death of cardiac stem cells","volume":"113","author":"Piero","year":"2006","journal-title":"Circulation"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1161\/01.RES.0000150856.47324.5b","article-title":"Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction","volume":"95","author":"Kucia","year":"2004","journal-title":"Circ. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/nature02446","article-title":"Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts","volume":"428","author":"Murry","year":"2004","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature13309","article-title":"C-kit+ cells minimally contribute cardiomyocytes to the heart","volume":"509","author":"Kanisicak","year":"2014","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/jamacardio.2016.2225","article-title":"Adult stem cell therapy and heart failure, 2000 to 2016: A systematic review","volume":"1","author":"Nguyen","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.yjmcc.2010.08.005","article-title":"Paracrine mechanisms of stem cell reparative and regenerative actions in the heart","volume":"50","author":"Mirotsou","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.jacc.2011.11.029","article-title":"Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells","volume":"59","author":"Li","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1478-811X-9-12","article-title":"Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC","volume":"9","author":"Hass","year":"2011","journal-title":"Cell Commun. Signal."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1161\/CIRCRESAHA.116.310494","article-title":"Concurrent isolation of 3 distinct cardiac stem cell populations from a single human heart biopsy","volume":"121","author":"Monsanto","year":"2017","journal-title":"Circ. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1001\/jama.2012.25321","article-title":"Comparison of allogeneic vs autologous bone marrow\u2013derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy","volume":"308","author":"Hare","year":"2012","journal-title":"JAMA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/xen.12000","article-title":"Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation","volume":"19","author":"Li","year":"2012","journal-title":"Xenotransplantation"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.expneurol.2004.06.023","article-title":"Transplantation of pig stem cells into rat brain: Proliferation during the first 8 weeks","volume":"190","author":"Medicetty","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.transproceed.2008.02.012","article-title":"Intra-bone marrow cotransplantation of donor mesenchymal stem cells in pig-to-NOD\/SCID mouse bone marrow transplantation facilitates short-term xenogeneic hematopoietic engraftment","volume":"40","author":"Eguchi","year":"2008","journal-title":"Transpl. Proc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1634\/stemcells.2006-0168","article-title":"Xenotransplantation of long-term-cultured swine bone marrow-derived mesenchymal stem cells","volume":"25","author":"Nakamura","year":"2007","journal-title":"Stem Cells Dayt. Ohio"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"78","DOI":"10.2174\/1574888X10666150723145911","article-title":"Research advancements in porcine derived mesenchymal stem cells","volume":"11","author":"Bharti","year":"2016","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Karpov, A.A., Udalova, D.V., Pliss, M.G., and Galagudza, M.M. (2016). Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells. Cell Prolif., 50.","DOI":"10.1111\/cpr.12316"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.ymthe.2018.05.009","article-title":"Mesenchymal stem cell-based therapy for cardiovascular disease: Progress and challenges","volume":"26","author":"Bagno","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.transproceed.2004.12.247","article-title":"Differentiation \u201cin vitro\u201d of primary and immortalized porcine mesenchymal stem cells into cardiomyocytes for cell transplantation","volume":"37","author":"Moscoso","year":"2005","journal-title":"Transpl. Proc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"14022","DOI":"10.1073\/pnas.0903201106","article-title":"Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity","volume":"106","author":"Quevedo","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"765846","DOI":"10.1155\/2015\/765846","article-title":"A new paradigm in cardiac regeneration: The mesenchymal stem cell secretome","volume":"2015","author":"Gallina","year":"2015","journal-title":"Stem Cells Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"28250","DOI":"10.1038\/srep28250","article-title":"Bone marrow mesenchymal stem cells (BM-MSCs) improve heart function in swine myocardial infarction model through paracrine effects","volume":"6","author":"Cai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1016\/j.jacc.2017.09.036","article-title":"A combination of allogeneic stem cells promotes cardiac regeneration","volume":"70","author":"Natsumeda","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1161\/CIRCULATIONAHA.112.131110","article-title":"Enhanced effect of human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and restore cardiac function after myocardial infarction","volume":"127","author":"Williams","year":"2013","journal-title":"Circulation"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1016\/j.jacc.2015.08.879","article-title":"Synergistic effects of combined cell therapy for chronic ischemic cardiomyopathy","volume":"66","author":"Karantalis","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1161\/CIRCRESAHA.117.312486","article-title":"Preclinical studies of stem cell therapy for heart disease","volume":"122","author":"Tompkins","year":"2018","journal-title":"Circ. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nature13233","article-title":"Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts","volume":"510","author":"Chong","year":"2014","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1161\/CIRCRESAHA.117.311578","article-title":"Lack of remuscularization following transplantation of human embryonic stem cell-derived cardiovascular progenitor cells in infarcted nonhuman primates","volume":"122","author":"Keyang","year":"2018","journal-title":"Circ. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nature19815","article-title":"Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts","volume":"538","author":"Shiba","year":"2016","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1161\/ATVBAHA.109.189662","article-title":"Combined therapy with simvastatin and bone marrow\u2013derived mesenchymal stem cells increases benefits in infarcted swine hearts","volume":"29","author":"Ji","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Bobi, J., Solanes, N., Fern\u00e1ndez-Jim\u00e9nez, R., Gal\u00e1n-Arriola, C., Dantas, A.P., Fern\u00e1ndez-Friera, L., G\u00e1lvez-Mont\u00f3n, C., Rigol-Monz\u00f3, E., Ag\u00fcero, J., and Ram\u00edrez, J. (2017). Intracoronary administration of allogeneic adipose tissue\u2014Derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function, in a translational model of acute myocardial infarction. J. Am. Heart Assoc. Cardiovasc. Cereb. Dis., 6.","DOI":"10.1161\/JAHA.117.005771"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13287-016-0350-z","article-title":"Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model","volume":"7","author":"Moscoso","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.jacbts.2016.06.005","article-title":"A cell-enriched engineered myocardial graft limits infarct size and improves cardiac function: Pre-clinical study in the porcine myocardial infarction model","volume":"1","author":"Roura","year":"2016","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11474","DOI":"10.1073\/pnas.0504388102","article-title":"Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction","volume":"102","author":"Amado","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1111\/1755-5922.12037","article-title":"eNOS overexpressing bone marrow cells are safe and effective in a porcine model of myocardial regeneration following acute myocardial infarction","volume":"31","author":"Ward","year":"2013","journal-title":"Cardiovasc. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.3346\/jkms.2017.32.10.1708","article-title":"Intramyocardial injection of stem cells in pig myocardial infarction model: The first trial in korea","volume":"32","author":"Kim","year":"2017","journal-title":"J. Korean Med. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1016\/S0003-4975(02)03517-8","article-title":"Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects","volume":"73","author":"Shake","year":"2002","journal-title":"Ann. Thorac. Surg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2007.02.035","article-title":"Neovascularization and cardiomyocytes regeneration in acute myocardial infarction after bone marrow stromal cell transplantation: Comparison of infarct-relative and noninfarct-relative arterial approaches in swine","volume":"381","author":"Yang","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1046\/j.1540-8167.2003.03124.x","article-title":"Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction","volume":"14","author":"Pak","year":"2003","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1161\/CIRCRESAHA.115.306850","article-title":"Comparative efficacy of intracoronary allogeneic mesenchymal stem cells and cardiosphere-derived cells in swine with hibernating myocardium","volume":"117","author":"Weil","year":"2015","journal-title":"Circ. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"186","DOI":"10.5966\/sctm.2015-0101","article-title":"Concise review: Review and perspective of cell dosage and routes of administration from preclinical and clinical studies of stem cell therapy for heart disease","volume":"5","author":"Golpanian","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Sheng, C.C., Zhou, L., and Hao, J. (2013). Current stem cell delivery methods for myocardial repair. Biomed. Res. Int.","DOI":"10.1155\/2013\/547902"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"I150","DOI":"10.1161\/CIRCULATIONAHA.104.526749","article-title":"Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: Implications for current clinical trials","volume":"112","author":"Hou","year":"2005","journal-title":"Circulation"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s13287-017-0695-y","article-title":"Mesenchymal stem cells for cardiac repair: Are the actors ready for the clinical scenario?","volume":"8","author":"Roura","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Perea-Gil, I., Prat-Vidal, C., and Bayes-Genis, A. (2015). In vivo experience with natural scaffolds for myocardial infarction: The times they are a-changin\u2019. Stem Cell Res. Ther., 6.","DOI":"10.1186\/s13287-015-0237-4"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13036-019-0185-0","article-title":"Cardiac tissue engineering: State-of-the-art methods and outlook","volume":"13","author":"Nguyen","year":"2019","journal-title":"J. Biol. Eng."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"647","DOI":"10.5966\/sctm.2016-0063","article-title":"Noninvasive assessment of an engineered bioactive graft in myocardial infarction: Impact on cardiac function and scar healing","volume":"6","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"16206","DOI":"10.1038\/s41598-018-33946-2","article-title":"A thin layer of decellularized porcine myocardium for cell delivery","volume":"8","author":"Shah","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1159\/000331400","article-title":"Right ventricular outflow tract repair with a cardiac biologic scaffold","volume":"195","author":"Wainwright","year":"2012","journal-title":"Cells Tissues Organs"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"G\u00e1lvez-Mont\u00f3n, C., Fernandez-Figueras, M.T., Mart\u00ed, M., Soler-Botija, C., Roura, S., Perea-Gil, I., Prat-Vidal, C., Lluci\u00e0-Valldeperas, A., Raya, \u00c1., and Bayes-Genis, A. (2015). Neoinnervation and neovascularization of acellular pericardial-derived scaffolds in myocardial infarcts. Stem Cell Res. Ther., 6.","DOI":"10.1186\/s13287-015-0101-6"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.healun.2016.01.012","article-title":"Epicardial infarct repair with bioinductive extracellular matrix promotes vasculogenesis and myocardial recovery","volume":"35","author":"Mewhort","year":"2016","journal-title":"J. Heart Lung Transpl."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Schmuck, E.G., Hematti, P., and Raval, A.N. (2018). Natural sources of extracellular matrix for cardiac repair. Cardiac Extracellular Matrix: Fundamental Science to Clinical Applications, Springer International Publishing. Advances in Experimental Medicine and Biology.","DOI":"10.1007\/978-3-319-97421-7"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.jss.2012.04.042","article-title":"Toll-like receptor 4 ablation improves stem cell survival after hypoxic injury","volume":"177","author":"Brewster","year":"2012","journal-title":"J. Surg. Res."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Wang, Y., Abarbanell, A.M., Herrmann, J.L., Weil, B.R., Manukyan, M.C., Poynter, J.A., and Meldrum, D.R. (2010). TLR4 inhibits mesenchymal stem cell (MSC) STAT3 activation and thereby exerts deleterious effects on MSC\u2013mediated cardioprotection. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014206"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cardiores.2006.02.016","article-title":"The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model","volume":"70","author":"Lim","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11010-014-2188-y","article-title":"Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction","volume":"397","author":"Mao","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1089\/scd.2011.0674","article-title":"Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue","volume":"21","author":"Hsiao","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Hnatiuk, A.P., Ong, S., Olea, F.D., Locatelli, P., Riegler, J., Lee, W.H., Jen, C.H., De Lorenzi, A., Gim\u00e9nez, C.S., and Laguens, R. (2016). Allogeneic mesenchymal stromal cells overexpressing mutant human hypoxia-inducible factor 1-\u03b1 (HIF1-\u03b1) in an ovine model of acute myocardial infarction. J. Am. Heart Assoc. Cardiovasc. Cereb. Dis., 5.","DOI":"10.1161\/JAHA.116.003714"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/mt.2010.301","article-title":"Hypoxia-inducible vascular endothelial growth factor-engineered mesenchymal stem cells prevent myocardial ischemic injury","volume":"19","author":"Kim","year":"2011","journal-title":"Mol. Ther. J. Am. Soc. Gene"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nm.4313","article-title":"Refining strategies to translate genome editing to the clinic","volume":"23","author":"Cornu","year":"2017","journal-title":"Nat. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/FJC.0000000000000183","article-title":"MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart","volume":"65","author":"Dakhlallah","year":"2015","journal-title":"J. Cardiovasc. Pharm."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Lee, C.Y., Shin, S., Lee, J., Seo, H.-H., Lim, K.H., Kim, H., Choi, J.-W., Kim, S.W., Lee, S., and Lim, S. (2016). MicroRNA-mediated down-regulation of apoptosis signal-regulating kinase 1 (ASK1) attenuates the apoptosis of human mesenchymal stem cells (MSCs) transplanted into infarcted heart. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101752"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1161\/CIRCULATIONAHA.111.017954","article-title":"Novel microRNA pro-survival cocktail for improving engraftment and function of cardiac progenitor cell transplantation","volume":"124","author":"Hu","year":"2011","journal-title":"Circulation"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3892\/ijmm.2012.1200","article-title":"Mesenchymal stem cells modified with miR-126 release angiogenic factors and activate Notch ligand Delta-like-4, enhancing ischemic angiogenesis and cell survival","volume":"31","author":"Huang","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000461596","article-title":"Exogenous miRNA-146a enhances the therapeutic efficacy of human mesenchymal stem cells by increasing vascular endothelial growth factor secretion in the ischemia\/reperfusion-injured heart","volume":"54","author":"Seo","year":"2017","journal-title":"J. Vasc. Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"E2785","DOI":"10.1073\/pnas.1424042112","article-title":"Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes","volume":"112","author":"Kuppusamy","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12929-017-0337-9","article-title":"Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway","volume":"24","author":"Shen","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.bbrc.2012.03.092","article-title":"MiR-499 induces cardiac differentiation of rat mesenchymal stem cells through wnt\/\u03b2-catenin signaling pathway","volume":"420","author":"Zhang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13287-019-1237-6","article-title":"Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells","volume":"10","author":"Crisostomo","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1161\/CIRCRESAHA.118.312823","article-title":"Safety and efficacy of intracoronary infusion of allogeneic human cardiac stem cells in patients with st-segment elevation myocardial infarction and left ventricular dysfunction","volume":"123","author":"Bogaert","year":"2018","journal-title":"Circ. Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1909346","DOI":"10.1155\/2018\/1909346","article-title":"Recent progress in stem cell modification for cardiac regeneration","volume":"2018","author":"Lemcke","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1186\/s12967-019-02136-7","article-title":"The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: A systematic review","volume":"17","author":"Bahsoun","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Stevens, S. (2019). Genome engineering for xenotransplantation. Genet. Eng. Glimpse Tech. Appl.","DOI":"10.5772\/intechopen.84782"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature01079","article-title":"Somatic cell nuclear transfer","volume":"419","author":"Wilmut","year":"2002","journal-title":"Nature"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1038\/ncomms4903","article-title":"Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance","volume":"5","author":"Meyer","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/scd.2014.0136","article-title":"Do human leukocyte antigen-typed cellular therapeutics based on induced pluripotent stem cells make commercial sense?","volume":"24","author":"Bravery","year":"2014","journal-title":"Stem Cells Dev."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nbt0708-739","article-title":"HLA-haplotype banking and iPS cells","volume":"26","author":"Nakatsuji","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-019-0578-x","article-title":"Human iPSC banking: Barriers and opportunities","volume":"26","author":"Huang","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_163","unstructured":"Ratajczak, M.Z. (2019). Genomic instability of iPSCs and challenges in their clinical applications. Stem Cells: Therapeutic Applications, Springer International Publishing. Advances in Experimental Medicine and Biology."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cell.2016.12.036","article-title":"Interspecies chimerism with mammalian pluripotent stem cells","volume":"168","author":"Wu","year":"2017","journal-title":"Cell"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/medethics-2018-105227","article-title":"Moral uncertainty and the farming of human-pig chimeras","volume":"45","author":"Koplin","year":"2019","journal-title":"J. Med. Ethics"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/rb\/rbz017","article-title":"Cardiac tissue-derived extracellular matrix scaffolds for myocardial repair: Advantages and challenges","volume":"6","author":"Pawan","year":"2019","journal-title":"Regen. Biomater."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Huang, K., Ozpinar, E.W., Su, T., Tang, J., Shen, D., Qiao, L., Hu, S., Li, Z., Liang, H., and Mathews, K. (2020). An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aat9683"},{"key":"ref_168","first-page":"60283D","article-title":"Human versus porcine tissue sourcing for an injectable myocardial matrix hydrogel","volume":"2014","author":"Johnson","year":"2014","journal-title":"Biomater. Sci."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.jacbts.2019.07.012","article-title":"First-in-man study of a cardiac extracellular matrix hydrogel in early and late myocardial infarction patients","volume":"4","author":"Traverse","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ijsu.2015.09.051","article-title":"Regulatory aspects of clinical xenotransplantation","volume":"23","author":"Schuurman","year":"2015","journal-title":"Int. J. Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:10Z","timestamp":1760179630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":170,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249686"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249686","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}