{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:18:12Z","timestamp":1780431492923,"version":"3.54.1"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>The only curative therapy for many endstage diseases is allograft organ transplantation. Due to the limited supply of donor organs, relatively few patients are recipients of a transplanted organ. Therefore, new strategies are warranted to address this unmet need. Using gene editing technologies, somatic cell nuclear transfer and human induced pluripotent stem cell technologies, interspecies chimeric organs have been pursued with promising results. In this review, we highlight the overall technical strategy, the successful early results and the hurdles that need to be addressed in order for these approaches to produce a successful organ that could be transplanted in patients with endstage diseases.<\/jats:p>","DOI":"10.3389\/fcell.2022.1065536","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T11:57:09Z","timestamp":1670500629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Blastocyst complementation and interspecies chimeras in gene edited pigs"],"prefix":"10.3389","volume":"10","author":[{"given":"Yong-ho","family":"Choe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Sorensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Garry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary G.","family":"Garry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e23","DOI":"10.1097\/TXD.0000000000000533","article-title":"Kidneys from \u03b11, 3-galactosyltransferase knockout\/human heme oxygenase-1\/human A20 transgenic pigs are protected from rejection during ex vivo perfusion with human blood","volume":"1","author":"Ahrens","year":"2015","journal-title":"Transpl. Direct"},{"key":"B2","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1146\/annurev.immunol.16.1.433","article-title":"Xenogeneic transplantation","volume":"16","author":"Auchincloss","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1001\/jama.1985.03360230053022","article-title":"Baboon-to-human cardiac xenotransplantation in a neonate","volume":"254","author":"Bailey","year":"1985","journal-title":"Jama"},{"key":"B4","article-title":"Minature swine uses in biomedical research","volume-title":"Sinclair bio resources","author":"Bouchard","year":"2019"},{"key":"B5","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/380064a0","article-title":"Sheep cloned by nuclear transfer from a cultured cell line","volume":"380","author":"Campbell","year":"1996","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1126\/science.22.563.473-a","article-title":"The university of Florida","volume":"22","author":"Carrel","year":"1905","journal-title":"Funct. a transplanted kidney Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1084\/jem.9.2.226","article-title":"Heterotransplantation of blood vessels preserved in cold storage","volume":"9","author":"Carrel","year":"1907","journal-title":"J. Exp. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1084\/jem.20.1.1","article-title":"Present condition of A strain of connective tissue twenty-eight months old","volume":"60","author":"Carrel","year":"1914","journal-title":"Exp. operations orifices heart Ann Surg"},{"key":"B9","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1084\/jem.15.4.389","article-title":"Ultimate results of aortic transplantations","volume":"15","author":"Carrel","year":"1912","journal-title":"J. Exp. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.stem.2013.03.004","article-title":"Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner","volume":"12","author":"Chan","year":"2013","journal-title":"Cell Stem Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s11248-016-9996-7","article-title":"Production of heterozygous alpha 1, 3-galactosyltransferase (GGTA1) knock-out transgenic miniature pigs expressing human CD39","volume":"26","author":"Choi","year":"2017","journal-title":"Transgenic Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1080\/08998280.2012.11928783","article-title":"A brief history of cross-species organ transplantation","volume":"25","author":"Cooper","year":"2012","journal-title":"Proc.(Bayl Univ. Med. Cent."},{"key":"B14","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.ijsu.2015.06.060","article-title":"A brief history of clinical xenotransplantation","volume":"23","author":"Cooper","year":"2015","journal-title":"Int. J. Surg."},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1682\/JRRD.2014.07.0165","article-title":"Volumetric muscle loss leads to permanent disability following extremity trauma","volume":"52","author":"Corona","year":"2015","journal-title":"J. Rehabil. Res. Dev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1161\/ATVBAHA.114.304768","article-title":"Etv2 and fli1b function together as key regulators of vasculogenesis and angiogenesis","volume":"35","author":"Craig","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1046\/j.1469-7580.1998.19310105.x","article-title":"Anatomy of the pig heart: Comparisons with normal human cardiac structure","volume":"193","author":"Crick","year":"1998","journal-title":"J. Anat."},{"key":"B19","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/evl3.122","article-title":"Molecular evolution across developmental time reveals rapid divergence in early embryogenesis","volume":"3","author":"Cutter","year":"2019","journal-title":"Evol. Lett."},{"key":"B20","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/s41587-019-0373-y","article-title":"Generation of human endothelium in pig embryos deficient in ETV2","volume":"38","author":"Das","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"Genome editing. The new frontier of genome engineering with CRISPR-Cas9","volume":"346","author":"Doudna","year":"2014","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"29081","DOI":"10.1038\/srep29081","article-title":"Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing","volume":"6","author":"Fischer","year":"2016","journal-title":"Sci. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s13238-019-00676-8","article-title":"Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs","volume":"11","author":"Fu","year":"2020","journal-title":"Protein Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"F23","DOI":"10.1530\/REP-21-0006","article-title":"25th Anniversary of Cloning by Somatic-Cell Nuclear Transfer: Current applications of SCNT in advanced breeding and genome editing in livestock","volume":"162","author":"Galli","year":"2021","journal-title":"Reproduction"},{"key":"B107","doi-asserted-by":"crossref","DOI":"10.19056\/ijmdsjssmes\/2013\/v2i2\/86776","article-title":"A gross comparative anatomical study of hearts in human cadavers and pigs","volume":"2","author":"Garg","year":"2013","journal-title":"IJMDS"},{"key":"B25","first-page":"212","article-title":"Etv2 is a master regulator of hematoendothelial lineages","volume":"127","author":"Garry","year":"2016","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"B26","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1161\/CIRCRESAHA.118.314189","article-title":"Interspecies chimeras and the generation of humanized organs","volume":"124","author":"Garry","year":"2019","journal-title":"Circ. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1177\/15353702211024948","article-title":"Interspecies chimeras as a platform for exogenic organ production and transplantation","volume":"246","author":"Garry","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/00000441-200508000-00006","article-title":"Alternative therapies for orthotopic heart transplantation","volume":"330","author":"Garry","year":"2005","journal-title":"Am. J. Med. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"10709","DOI":"10.1038\/s41598-020-66430-x","article-title":"Heterotopic porcine cardiac xenotransplantation in the intra-abdominal position in a non-human primate model","volume":"10","author":"Goerlich","year":"2020","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"01261","DOI":"10.1016\/j.jtcvs.2021.07.051","article-title":"The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors","author":"Goerlich","year":"2021","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"B31","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41556-022-00901-3","article-title":"ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage","volume":"24","author":"Gong","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"14362","DOI":"10.1038\/ncomms14362","article-title":"Dpath software reveals hierarchical haemato-endothelial lineages of Etv2 progenitors based on single-cell transcriptome analysis","volume":"8","author":"Gong","year":"2017","journal-title":"Nat. Commun."},{"key":"B33","volume-title":"Blacksburg company raised genetically modified pig for first heart transplant in human","author":"Graham","year":"2022"},{"key":"B34","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1159\/000444673","article-title":"Regenerative and rehabilitative medicine: A necessary synergy for functional recovery from volumetric muscle loss injury","volume":"202","author":"Greising","year":"2016","journal-title":"Cells Tissues Organs"},{"key":"B35","doi-asserted-by":"publisher","first-page":"13179","DOI":"10.1038\/s41598-017-13306-2","article-title":"Unwavering pathobiology of volumetric muscle loss injury","volume":"7","author":"Greising","year":"2017","journal-title":"Sci. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1056\/NEJMoa2201422","article-title":"Genetically modified porcine-to-human cardiac xenotransplantation","volume":"387","author":"Griffith","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3389\/fgene.2015.00293","article-title":"Efficacy of the porcine species in biomedical research","volume":"6","author":"Gutierrez","year":"2015","journal-title":"Front. Genet."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1001\/jama.1964.03060390034008","article-title":"Heart transplantation in man: Developmental studies and report of a case","volume":"188","author":"Hardy","year":"1964","journal-title":"Jama"},{"key":"B39","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/364501a0","article-title":"Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene","volume":"364","author":"Hasty","year":"1993","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e12664","DOI":"10.1111\/xen.12664","article-title":"Growth hormone receptor knockout to reduce the size of donor pigs for preclinical xenotransplantation studies","volume":"28","author":"Hinrichs","year":"2021","journal-title":"Xenotransplantation"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1111\/j.1600-6143.2008.02444.x","article-title":"Rejection of cardiac xenografts transplanted from alpha1, 3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons","volume":"8","author":"Hisashi","year":"2008","journal-title":"Am. J. Transpl."},{"key":"B108","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.dci.2009.09.006","article-title":"Swine leukocyte antigen (SLA) diversity in Sinclair and Hanford swine","volume":"34","author":"Ho","year":"2010","journal-title":"Dev. Comp. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/xen.12167","article-title":"Pig-to-baboon heterotopic heart transplantation\u2013exploratory 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":"B43","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"B44","volume-title":"The merck veterinary manual","author":"Kahn","year":"2005"},{"key":"B45","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nature02876","article-title":"Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice","volume":"431","author":"Kassar-Duchossoy","year":"2004","journal-title":"Nature"},{"key":"B46","article-title":"Chapter 18 - in vitro and in vivo animal models: The engineering towards understanding human diseases and therapeutic interventions","volume-title":"Omics technologies and bio-engineering","author":"Khan","year":"2018"},{"key":"B47","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.cell.2010.07.039","article-title":"Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells","volume":"142","author":"Kobayashi","year":"2010","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"7335","DOI":"10.1073\/pnas.0307819101","article-title":"Production of alpha-1, 3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations","volume":"101","author":"Kolber-Simonds","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1093\/cvr\/cvx133","article-title":"Etv2 as an essential regulator of mesodermal lineage development","volume":"113","author":"Koyano-Nakagawa","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"28107","DOI":"10.1074\/jbc.M115.662197","article-title":"Feedback mechanisms regulate ets variant 2 (Etv2) gene expression and hematoendothelial lineages","volume":"290","author":"Koyano-Nakagawa","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/emmm.201201235","article-title":"Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf","volume":"5","author":"Labi","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1126\/science.1068228","article-title":"Production of alpha-1, 3-galactosyltransferase knockout pigs by nuclear transfer cloning","volume":"295","author":"Lai","year":"2002","journal-title":"Science"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1172\/JCI2134","article-title":"The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants","volume":"101","author":"Lin","year":"1998","journal-title":"J. Clin. Invest."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e935338","DOI":"10.12659\/AOT.935338","article-title":"Cardiac and pulmonary histopathology in baboons following genetically-engineered pig orthotopic heart transplantation","volume":"27","author":"Litovsky","year":"2022","journal-title":"Ann. Transpl."},{"key":"B55","doi-asserted-by":"publisher","first-page":"eabi6178","DOI":"10.1126\/sciadv.abi6178","article-title":"Evolutionary epigenomic analyses in mammalian early embryos reveal species-specific innovations and conserved principles of imprinting","volume":"7","author":"Lu","year":"2021","journal-title":"Sci. Adv."},{"key":"B109","doi-asserted-by":"publisher","first-page":"eabd5758","DOI":"10.1126\/scitranslmed.abd5758","article-title":"Importance of the pig as a human biomedical model","volume":"13","author":"Lunney","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/s41551-021-00693-1","article-title":"Humanized skeletal muscle in MYF5\/MYOD\/MYF6-null pig embryos","volume":"5","author":"Maeng","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"B57","doi-asserted-by":"publisher","first-page":"9407","DOI":"10.1073\/pnas.95.16.9407","article-title":"Evolutionary parameters of the transcribed mammalian genome: An analysis of 2, 820 orthologous rodent and human sequences","volume":"95","author":"Makalowski","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B58","doi-asserted-by":"publisher","first-page":"4557","DOI":"10.1073\/pnas.1222902110","article-title":"Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs","volume":"110","author":"Matsunari","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B59","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.stemcr.2019.11.008","article-title":"Compensation of disabled organogeneses in genetically modified pig fetuses by blastocyst complementation","volume":"14","author":"Matsunari","year":"2020","journal-title":"Stem Cell Rep."},{"key":"B60","volume-title":"Swine as a model for cardiovascular research","author":"Mckenzie","year":"1996"},{"key":"B110","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0165-2427(94)90133-3","article-title":"Sinclair miniature swine: An animal model of human melanoma","volume":"43","author":"Misfeldt","year":"1994","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.stem.2020.11.019","article-title":"Generation of functional organs using a cell-competitive niche in intra- and inter-species rodent chimeras","volume":"28","author":"Nishimura","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1242\/dev.122.3.983","article-title":"PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum","volume":"122","author":"Offield","year":"1996","journal-title":"Development"},{"key":"B64","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/j.1399-3089.2009.00556.x","article-title":"Transgenic expression of the human A20 gene in cloned pigs provides protection against apoptotic and inflammatory stimuli","volume":"16","author":"Oropeza","year":"2009","journal-title":"Xenotransplantation"},{"key":"B111","first-page":"344","article-title":"The Yucatan miniature pig: Characterization and utilization in biomedical research","volume":"36","author":"Panepinto","year":"1986","journal-title":"Lab Anim. Sci."},{"key":"B65","article-title":"First successful pig-to-human heart transplant may offer new options for patients","author":"Pelc","year":"2022","journal-title":"Med. News Today"},{"key":"B66","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.1399-3089.2010.00573_7.x","article-title":"Generation and characterization of pigs transgenic for human hemeoxygenase\u20101 (hHO\u20101)","volume":"17","author":"Petersen","year":"2010","journal-title":"Xenotransplantation"},{"key":"B67","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/j.1399-3089.2009.00537.x","article-title":"Pigs transgenic for human thrombomodulin have elevated production of activated protein C","volume":"16","author":"Petersen","year":"2009","journal-title":"Xenotransplantation"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1161\/CIRCULATIONAHA.120.048186","article-title":"Progress toward cardiac xenotransplantation","volume":"142","author":"Pierson","year":"2020","journal-title":"Circulation"},{"key":"B69","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/35024082","article-title":"Cloned pigs produced by nuclear transfer from adult somatic cells","volume":"407","author":"Polejaeva","year":"2000","journal-title":"Nature"},{"key":"B70","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/dvg.22396","article-title":"Etv2 rescues Flk1 mutant embryoid bodies","volume":"51","author":"Rasmussen","year":"2013","journal-title":"Genesis"},{"key":"B71","doi-asserted-by":"publisher","first-page":"e50103","DOI":"10.1371\/journal.pone.0050103","article-title":"VEGF\/Flk1 signaling cascade transactivates Etv2 gene expression","volume":"7","author":"Rasmussen","year":"2012","journal-title":"PLoS One"},{"key":"B72","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1006\/dbio.1995.0004","article-title":"Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis","volume":"172","author":"Rawls","year":"1995","journal-title":"Dev. Biol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1242\/dev.125.13.2349","article-title":"Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double mutant mice","volume":"125","author":"Rawls","year":"1998","journal-title":"Development"},{"key":"B74","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/d41586-022-00111-9","article-title":"First pig-to-human heart transplant: What can scientists learn?","volume":"601","author":"Reardon","year":"2022","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1097\/TP.0000000000003588","article-title":"Pathways to clinical cardiac xenotransplantation","volume":"105","author":"Reichart","year":"2021","journal-title":"Transplantation"},{"key":"B112","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.theriogenology.2016.04.055","article-title":"Comparative aspects of rodent and nonrodent animal models for mechanistic and translational diabetes research","volume":"86","author":"Renner","year":"2016","journal-title":"Theriogenology"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/0092-8674(93)90621-v","article-title":"MyoD or Myf-5 is required for the formation of skeletal muscle","volume":"75","author":"Rudnicki","year":"1993","journal-title":"Cell"},{"key":"B77","doi-asserted-by":"publisher","first-page":"S220","DOI":"10.1513\/AnnalsATS.201607-534MG","article-title":"Immune tolerance, xenografts, and large-animal studies in transplantation","volume":"14","author":"Sachs","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1097\/00007890-199806270-00006","article-title":"Orthotopic heart transplantation in a transgenic pig-to-primate model","volume":"65","author":"Schmoeckel","year":"1998","journal-title":"Transplantation"},{"key":"B79","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1111\/aor.14203","article-title":"First successful porcine to human heart transplantation performed in the United States","volume":"46","author":"Shah","year":"2022","journal-title":"Artif. Organs"},{"key":"B80","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ydbio.2014.02.018","article-title":"Cooperative interaction of Etv2 and Gata2 regulates the development of endothelial and hematopoietic lineages","volume":"389","author":"Shi","year":"2014","journal-title":"Dev. Biol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"9614","DOI":"10.1074\/jbc.M114.614628","article-title":"The transcription factor Mesp1 interacts with cAMP-responsive element binding protein 1 (Creb1) and coactivates Ets variant 2 (Etv2) gene expression","volume":"290","author":"Shi","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B82","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1161\/ATVBAHA.120.314488","article-title":"ETV2 (ets variant transcription factor 2)-rhoj cascade regulates endothelial progenitor cell migration during embryogenesis","volume":"40","author":"Singh","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"e0189010","DOI":"10.1371\/journal.pone.0189010","article-title":"Etv2-miR-130a-Jarid2 cascade regulates vascular patterning during embryogenesis","volume":"12","author":"Singh","year":"2017","journal-title":"PLoS One"},{"key":"B84","doi-asserted-by":"publisher","first-page":"l4669","DOI":"10.1136\/bmj.l4669","article-title":"Leonard L Bailey: In 1984 he transplanted a baboon heart into a human infant known as \u201cBaby Fae\u201d","volume":"366","author":"Stafford","year":"2019","journal-title":"BMJ"},{"key":"B85","doi-asserted-by":"publisher","first-page":"239784731769636","DOI":"10.1177\/2397847317696367","article-title":"Comparative cardiovascular physiology and pathology in selected lineages of minipigs: Relation to drug safety evaluation","volume":"1","author":"Stricker-Krongrad","year":"2017","journal-title":"Toxicol. Res. Appl."},{"key":"B86","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1177\/0192623316641784","article-title":"The miniature swine as a model in experimental and translational medicine","volume":"44","author":"Stricker-Krongrad","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"B113","article-title":"Swine in the laboratory: surgery, anesthesia, imaging, and experimental techniques","author":"Swindle","year":"2016"},{"key":"B87","doi-asserted-by":"publisher","first-page":"eaau6298","DOI":"10.1126\/sciimmunol.aau6298","article-title":"Transplanting organs from pigs to humans","volume":"4","author":"Sykes","year":"2019","journal-title":"Sci. Immunol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/s0092-8674(00)80189-0","article-title":"Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and myf-5 act upstream of MyoD","volume":"89","author":"Tajbakhsh","year":"1997","journal-title":"Cell"},{"key":"B89","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B90","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"B91","doi-asserted-by":"publisher","first-page":"4496","DOI":"10.1242\/dev.157404","article-title":"Mechanisms of gene regulation in human embryos and pluripotent stem cells","volume":"144","author":"Theunissen","year":"2017","journal-title":"Development"},{"key":"B92","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1477-7827-1-98","article-title":"Cloning animals by somatic cell nuclear transfer-biological factors","volume":"1","author":"Tian","year":"2003","journal-title":"Reprod. Biol. Endocrinol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1006\/dbio.2000.9621","article-title":"Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4","volume":"219","author":"Valdez","year":"2000","journal-title":"Dev. Biol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart disease and stroke statistics-2021 update: A report from the American heart association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"B95","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/cr.2017.138","article-title":"Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis","volume":"28","author":"Wang","year":"2018","journal-title":"Cell Res."},{"key":"B96","doi-asserted-by":"publisher","first-page":"e12552","DOI":"10.1111\/xen.12552","article-title":"Intra-bone bone marrow transplantation from hCD47 transgenic pigs to baboons prolongs chimerism to >60 days and promotes increased porcine lung transplant survival","volume":"27","author":"Watanabe","year":"2020","journal-title":"Xenotransplantation"},{"key":"B97","first-page":"1201","article-title":"Life-supporting pig-to-baboon heart xenotransplantation","volume":"17","author":"Waterworth","year":"1998","journal-title":"J. Heart Lung Transpl."},{"key":"B98","doi-asserted-by":"publisher","first-page":"e4840","DOI":"10.7717\/peerj.4840","article-title":"Divergent and convergent evolution of housekeeping genes in human-pig lineage","volume":"6","author":"Wei","year":"2018","journal-title":"PeerJ"},{"key":"B99","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/385810a0","article-title":"Viable offspring derived from fetal and adult mammalian cells","volume":"385","author":"Wilmut","year":"1997","journal-title":"Nature"},{"key":"B100","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1089\/clo.2006.0002","article-title":"Viable offspring derived from fetal and adult mammalian cells","volume":"9","author":"Wilmut","year":"2007","journal-title":"Cloning Stem Cells"},{"key":"B101","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/rda.12796","article-title":"Generation of human organs in pigs via interspecies blastocyst complementation","volume":"51","author":"Wu","year":"2016","journal-title":"Reprod. Domest. Anim."},{"key":"B102","doi-asserted-by":"publisher","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":"B103","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/nm1172","article-title":"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","volume":"11","author":"Yamada","year":"2005","journal-title":"Nat. Med."},{"key":"B104","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nature21070","article-title":"Interspecies organogenesis generates autologous functional islets","volume":"542","author":"Yamaguchi","year":"2017","journal-title":"Nature"},{"key":"B105","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41586-021-03273-0","article-title":"Cell competition constitutes a barrier for interspecies chimerism","volume":"592","author":"Zheng","year":"2021","journal-title":"Nature"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.stemcr.2022.03.009","article-title":"Generating functional cells through enhanced interspecies chimerism with human pluripotent stem cells","volume":"17","author":"Zhu","year":"2022","journal-title":"Stem Cell Rep."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.1065536\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T11:57:17Z","timestamp":1670500637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.1065536\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":112,"alternative-id":["10.3389\/fcell.2022.1065536"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.1065536","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"article-number":"1065536"}}