{"id":"https://openalex.org/W4408949385","doi":"https://doi.org/10.3389/frtra.2025.1559512","title":"The current issues of translating clinical xenokidney transplantation, with an emphasis on prevention of rejection","display_name":"The current issues of translating clinical xenokidney transplantation, with an emphasis on prevention of rejection","publication_year":2025,"publication_date":"2025-03-28","ids":{"openalex":"https://openalex.org/W4408949385","doi":"https://doi.org/10.3389/frtra.2025.1559512","pmid":"https://pubmed.ncbi.nlm.nih.gov/40224288"},"language":"en","primary_location":{"id":"doi:10.3389/frtra.2025.1559512","doi":"https://doi.org/10.3389/frtra.2025.1559512","is_oa":true,"landing_page_url":"https://doi.org/10.3389/frtra.2025.1559512","pdf_url":null,"source":{"id":"https://openalex.org/S4387280090","display_name":"Frontiers in Transplantation","issn_l":"2813-2440","issn":["2813-2440"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Transplantation","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3389/frtra.2025.1559512","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5007319566","display_name":"Jean Kwun","orcid":"https://orcid.org/0000-0002-8563-5472","observed_orcids":["https://orcid.org/0000-0002-8563-5472"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]},{"id":"https://openalex.org/I4210126298","display_name":"Duke Medical Center","ror":"https://ror.org/03njmea73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210126298","https://openalex.org/I4210144876"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jean Kwun","raw_affiliation_strings":["Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States","institution_ids":["https://openalex.org/I170897317","https://openalex.org/I4210126298"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053124974","display_name":"Joseph M. Ladowski","orcid":"https://orcid.org/0000-0002-6787-3725","observed_orcids":["https://orcid.org/0000-0002-6787-3725"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]},{"id":"https://openalex.org/I4210126298","display_name":"Duke Medical Center","ror":"https://ror.org/03njmea73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210126298","https://openalex.org/I4210144876"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph M. Ladowski","raw_affiliation_strings":["Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States","institution_ids":["https://openalex.org/I170897317","https://openalex.org/I4210126298"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013219628","display_name":"Annette M. Jackson","orcid":"https://orcid.org/0000-0003-2648-2944","observed_orcids":["https://orcid.org/0000-0003-2648-2944"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]},{"id":"https://openalex.org/I4210126298","display_name":"Duke Medical Center","ror":"https://ror.org/03njmea73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210126298","https://openalex.org/I4210144876"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Annette M. Jackson","raw_affiliation_strings":["Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States","institution_ids":["https://openalex.org/I170897317","https://openalex.org/I4210126298"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5078530019","display_name":"Stuart J. Knechtle","orcid":"https://orcid.org/0000-0002-1625-385X","observed_orcids":["https://orcid.org/0000-0002-1625-385X"]},"institutions":[{"id":"https://openalex.org/I170897317","display_name":"Duke University","ror":"https://ror.org/00py81415","country_code":"US","type":"education","lineage":["https://openalex.org/I170897317"]},{"id":"https://openalex.org/I4210126298","display_name":"Duke Medical Center","ror":"https://ror.org/03njmea73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210126298","https://openalex.org/I4210144876"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Stuart Knechtle","raw_affiliation_strings":["Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States","institution_ids":["https://openalex.org/I170897317","https://openalex.org/I4210126298"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":1950,"currency":"CHF","value_usd":2353},"apc_paid":{"value":1950,"currency":"CHF","value_usd":2353},"fwci":2.6772,"has_fulltext":false,"cited_by_count":3,"citation_normalized_percentile":{"value":0.8857273,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":97},"biblio":{"volume":"4","issue":null,"first_page":"1559512","last_page":"1559512"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12654","display_name":"Xenotransplantation and immune response","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T12654","display_name":"Xenotransplantation and immune response","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10373","display_name":"Renal Transplantation Outcomes and Treatments","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2747","display_name":"Transplantation"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10999","display_name":"Organ Transplantation Techniques and Outcomes","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/xenotransplantation","display_name":"xenotransplantation","score":0.9700000286102295},{"id":"https://openalex.org/keywords/genetically-modified-pigs","display_name":"genetically modified pigs","score":0.8309999704360962},{"id":"https://openalex.org/keywords/immunosuppression","display_name":"immunosuppression","score":0.722000002861023},{"id":"https://openalex.org/keywords/regulatory-approval","display_name":"regulatory approval","score":0.3790000081062317},{"id":"https://openalex.org/keywords/organ-shortage","display_name":"organ shortage","score":0.5899999737739563},{"id":"https://openalex.org/keywords/end-stage-renal-disease","display_name":"end-stage renal disease","score":0.6150000095367432},{"id":"https://openalex.org/keywords/nonhuman-primates","display_name":"non-human primates","score":0.5630000233650208},{"id":"https://openalex.org/keywords/xenograft-survival","display_name":"xenograft survival","score":0.5329999923706055}],"concepts":[{"id":"https://openalex.org/C177454536","wikidata":"https://www.wikidata.org/wiki/Q578290","display_name":"Emphasis (telecommunications)","level":2,"score":0.7349951267242432},{"id":"https://openalex.org/C148043351","wikidata":"https://www.wikidata.org/wiki/Q4456944","display_name":"Current (fluid)","level":2,"score":0.6428742408752441},{"id":"https://openalex.org/C2911091166","wikidata":"https://www.wikidata.org/wiki/Q106419912","display_name":"Transplantation","level":2,"score":0.6392288208007812},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5156289935112},{"id":"https://openalex.org/C177713679","wikidata":"https://www.wikidata.org/wiki/Q679690","display_name":"Intensive care medicine","level":1,"score":0.4515031576156616},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.26754868030548096},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.15974563360214233},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.14495524764060974},{"id":"https://openalex.org/C76155785","wikidata":"https://www.wikidata.org/wiki/Q418","display_name":"Telecommunications","level":1,"score":0.05590921640396118},{"id":"https://openalex.org/C119599485","wikidata":"https://www.wikidata.org/wiki/Q43035","display_name":"Electrical engineering","level":1,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.3389/frtra.2025.1559512","doi":"https://doi.org/10.3389/frtra.2025.1559512","is_oa":true,"landing_page_url":"https://doi.org/10.3389/frtra.2025.1559512","pdf_url":null,"source":{"id":"https://openalex.org/S4387280090","display_name":"Frontiers in Transplantation","issn_l":"2813-2440","issn":["2813-2440"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Transplantation","raw_type":"journal-article"},{"id":"pmid:40224288","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40224288","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in transplantation","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:11985775","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11985775","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Front Transplant","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:25897056ac5a4966889fd6d9387c8b79","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/25897056ac5a4966889fd6d9387c8b79","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Transplantation, Vol 4 (2025)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/frtra.2025.1559512","doi":"https://doi.org/10.3389/frtra.2025.1559512","is_oa":true,"landing_page_url":"https://doi.org/10.3389/frtra.2025.1559512","pdf_url":null,"source":{"id":"https://openalex.org/S4387280090","display_name":"Frontiers in Transplantation","issn_l":"2813-2440","issn":["2813-2440"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Transplantation","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.98580002784729,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"display_name":"Zero hunger","score":0.6299999952316284,"id":"https://metadata.un.org/sdg/2"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":16,"referenced_works":["https://openalex.org/W2163649189","https://openalex.org/W2315479515","https://openalex.org/W2316183034","https://openalex.org/W2903264420","https://openalex.org/W2919104334","https://openalex.org/W3036731060","https://openalex.org/W3185973121","https://openalex.org/W4205658126","https://openalex.org/W4211216709","https://openalex.org/W4280550957","https://openalex.org/W4283331743","https://openalex.org/W4300003801","https://openalex.org/W4385851807","https://openalex.org/W4387541325","https://openalex.org/W4406178443","https://openalex.org/W4407259548"],"related_works":["https://openalex.org/W2899084033","https://openalex.org/W2748952813","https://openalex.org/W3031052312","https://openalex.org/W4389568370","https://openalex.org/W3032375762","https://openalex.org/W1995515455","https://openalex.org/W2080531066","https://openalex.org/W3108674512","https://openalex.org/W1506200166","https://openalex.org/W2055105357"],"abstract_inverted_index":{"1.":[0,217,1310],"Current":[1,1489],"clinical":[2,52,119,143,207,233,288,339,355,442,476,492,738,871,939,1094,1189,1307,1490,1503,1604,1702,1737,1783,1833,1875,1974],"xenotransplantation":[3,57,208,290,424,452,488,505,780,793,913,1073,1342,1548,1705,1830,1876],"experienceFor":[4],"decades":[5],"xenotransplantation,":[6,1150,1372,1692],"the":[7,24,28,37,66,81,101,107,114,117,121,142,151,158,199,203,269,286,308,321,334,376,412,433,469,486,491,533,568,580,633,659,714,735,741,748,790,826,852,873,904,908,917,930,981,1031,1043,1092,1101,1117,1129,1136,1139,1144,1151,1162,1187,1246,1278,1292,1301,1305,1321,1409,1474,1506,1555,1558,1584,1592,1656,1682,1687,1731,1735,1742,1787,1793,1817,1821,1843,1863,1935,1945,1968,2045,2056,2072],"use":[8,240,1248],"of":[9,51,91,98,123,134,157,194,231,241,302,394,409,485,502,512,548,558,619,636,729,737,743,770,822,829,837,921,929,947,998,1033,1049,1052,1064,1078,1088,1105,1114,1131,1138,1175,1215,1224,1242,1249,1261,1266,1285,1294,1412,1415,1476,1542,1557,1615,1655,1691,1704,1755,1792,1827,1872,1890,1965,2049,2065,2067],"genetically":[10,171,1639,1977,2030],"modified":[11,1640,2031],"pigs":[12],"as":[13,19,198,229,275,314,606,851,880,1325,1373,1384,1459,1565,2052],"organ":[14,25,347,359,402,591,596,730,2057],"donors,":[15,592],"has":[16,30,583,1445,1550,1971,2024],"held":[17],"promise":[18],"a":[20,33,163,191,232,247,299,338,372,427,440,541,556,562,574,577,755,798,819,869,938,961,967,994,1018,1076,1097,1106,1173,1213,1221,1566,1589,1623,1745,1759,1800,1804,1870,2053],"potential":[21,557,866,919],"solution":[22,428,2054],"to":[23,86,184,221,429,543,566,573,599,626,641,681,684,699,701,722,758,783,787,809,835,856,863,882,937,990,1011,1028,1100,1116,1122,1161,1164,1220,1251,1273,1291,1300,1350,1363,1395,1407,1428,1472,1498,1544,1562,1588,1628,1699,1714,1719,1768,1785,1823,1883,1901,1997,2028,2036,2043,2055,2077],"shortage.":[26],"However,":[27,255,396,644,839,1334,1591],"field":[29,115,1549,1593,1818,2073],"recently":[31],"experienced":[32,1096,1911],"resurgence":[34,1098],"and":[35,56,95,130,136,277,296,307,325,392,404,406,462,495,509,514,532,570,621,709,724,763,772,884,898,910,1103,1125,1143,1147,1227,1288,1357,1432,1462,1501,1511,1534,1580,1643,1648,1678,1716,1722,1775,1789,1795,1832,1848,1860,1895,2047,2063],"in":[36,58,68,72,80,113,150,210,213,282,293,298,357,375,478,507,576,692,705,732,795,868,895,944,950,960,985,1068,1183,1212,1277,1304,1320,1341,1380,1387,1419,1425,1448,1493,1519,1525,1617,1632,1782,1799,1816,1903,1952,2007,2014],"last":[38],"two":[39,49,500,1896,1925,1973],"years":[40,186,418,1892],"witnessed":[41],"several":[42],"novel":[43],"medical":[44,252,523,749],"innovations":[45],"\u2013":[46,1110],"highlighted":[47],"by":[48,551,1235,1670,1856,1988,2021],"cases":[50,501,1831,1877,1948,1959],"human":[53,60,124,493,503,578,802,901,911,972,1275,1420,1477,1526,1572,1585,1603],"cardiac":[54,289,494,504],"xenografts":[55],"brain-dead":[59,590,652,672],"recipients":[61,607,1054],"(decedent":[62],"model)":[63],"1-3.":[64],"Undoubtedly,":[65],"success":[67,1553,1798],"extending":[69],"xenograft":[70,473,497,877,892,1014,1066,1158,1210,1351,1770,1913,1937],"survival":[71,216,300,391,511,984,996,1015,1124,1159,1166,1211,1422,1771,1826,1919,1938],"non-human":[73],"primates":[74],"(NHPs)":[75],"fostered":[76],"this":[77,170,224,256,430,588,986,1171,1865,2008],"translation.":[78],"Progress":[79,1647],"NHP":[82,952,1013,1053,1449,1559],"model":[83,582,965,1802],"is":[84,219,343,398,467,490,561,646,754,777,890,988,1026,1075,1135,1245,1361,1726,1835,1949],"attributed":[85],"1)":[87,1744],"additional":[88,131,280,971],"genetic":[89,132,145,195,1022],"modifications":[90],"pig":[92,144,173,189,323,800,909,969,1021,1748,1979,2032],"donors":[93],"4":[94],"2)":[96,1758],"availability":[97],"agents":[99,1176,1193,1312,1336],"targeting":[100,1177,1194,1313],"anti-CD40/CD154":[102],"signaling":[103],"pathway":[104,536],"5-7.":[105],"Despite":[106],"significant":[108,384,455,905,2075],"progress,":[109],"there":[110,397],"remains":[111,140,1399],"debate":[112],"regarding":[116,632,1583,1686,1752],"ideal":[118],"pig:":[120],"inclusion":[122],"complement":[125],"regulatory":[126,271,335,463],"proteins,":[127,129],"anti-inflammatory":[128],"mutations":[133],"glycans":[135],"SLAs.":[137],"Still,":[138],"consensus":[139],"that":[141,223,263,320,345,649,932,1035,1153,1297,1569,1730,1733,1765,1778,1814],"background":[146],"should":[147,933,1740],"possess":[148,1741],"nullifying-mutations":[149],"three":[152,159,1850,1947,1958,1998],"enzymes":[153],"responsible":[154],"for":[155,202,246,362,367,422,439,445,521,529,595,608,617,760,816,1371,1508,1807,1840,1976],"creation":[156],"known":[160],"xenoantigens":[161],"(i.e.":[162],"TKO":[164,799,968],"pig)":[165],"8.":[166],"Recent":[167],"outcomes":[168,313,744,828,949,959,1032],"with":[169,190,249,337,447,555,623,765,785,797,865,970,993,1167,1454,1521,1622,1634,1803,1885,1929,1934,1993,2000,2074],"edited":[172],"donor":[174,201,261,923,1020,1436,1641],"have":[175,328,539,1180,1337,1465,1485,1853,1878,1910],"demonstrated":[176],"impressively":[177],"prolonged":[178,766],"kidney":[179,373,481,1980,2002],"graft":[180,508,638,806,983,1040,1126,1410,1918],"survival,":[181,560,767],"lasting":[182],"up":[183,1996,2035],"2":[185,991,1059,1922],"9.":[187,814,977],"A":[188],"similar":[192,1019,1377],"level":[193],"modification":[196],"served":[197],"heart":[200,479,841],"historical":[204],"first":[205,1306,1736,1946,1985],"pig-to-human":[206,1874],"performed":[209,228],"2022,":[211],"resulting":[212,1145],"61-day":[214],"patient":[215,390,849,853,1888],"It":[218,1360,1725],"important":[220,888],"note":[222],"transplant":[225,374,2006,2029],"was":[226,527,1845,2010],"not":[227,259,265,329,655,833,846,1029,1037,1056,1230,1270,1338,1466,1486,1961],"part":[230],"trial,":[234,1986,2019],"but":[235,317,661,1233,1451],"rather":[236,662],"through":[237,1554],"an":[238,242,279,1203,1258,1598,1837,1886],"emergency":[239],"investigational":[243],"drug":[244,1134],"(eIND)":[245],"recipient":[248,510,1140,1228,1794],"no":[250,518,1693],"other":[251,346,519,1345,1381],"life-prolonging":[253,522],"options.":[254],"approval":[257,657,2027],"did":[258,1036,1055],"exclude":[260],"animals":[262,1034],"are":[264,436,604,615,832,1348,1368,1405,1620,1711,1960],"designated":[266],"pathogen-free.":[267],"Clearly,":[268],"federal":[270],"officials":[272],"viewed":[273],"it":[274,342,645,776,859,1025,1217,1398],"non-prohibitory":[276],"granted":[278],"eIND":[281],"September":[283,294],"2023.":[284],"Subsequently,":[285],"second":[287,2018],"took":[291],"place":[292],"2023":[295],"resulted":[297,506],"benefit":[301],"40":[303,515],"days.":[304,516],"Both":[305],"experts":[306],"general":[309],"public":[310],"accepted":[311],"these":[312,530,1335,1366,1390,1402,1630,2068],"successful":[315,1701,1723],"achievements":[316],"also":[318],"highlight":[319],"optimal":[322,1522],"genotype":[324],"immunosuppression":[326,976,1133,1244,1513,1523,1718],"regimen":[327,1120,1190,1764],"yet":[330],"been":[331,540,584,1181,1339,1446,1467,1487,1854,1879],"identified.":[332],"Given":[333,903],"issues":[336,471,943],"xenoheart":[340,1308],"study,":[341,1045],"likely":[344,538,847,1298],"systems":[348],"will":[349,781,860,1529,2070],"be":[350,426,675,696,720,746,861,934,1575,1607,1696],"looked":[351],"to.":[352],"The":[353,499,546,613,1061,1112,1547,1984,2004,2017,2060],"greatest":[354],"need":[356,1507],"solid":[358],"transplantation":[360,382,731,831,964,1573,1981,2051],"exists":[361],"end-stage":[363,448,2001],"renal":[364,449,496],"failure":[365,639,844,893],"patients,":[366,531],"which":[368],"over":[369,386],"90,000":[370],"await":[371],"United":[377,2022],"States":[378],"alone":[379,1404],"10.":[380],"Allo-kidney":[381],"offers":[383],"benefits":[385],"dialysis,":[387,825],"including":[388,457,1355,1750,1932],"improved":[389,768,1123],"quality":[393,769,821],"life.":[395],"huge":[399],"gap":[400],"between":[401,907],"supply":[403],"demand":[405],"approximately":[407],"40%":[408,805,1046],"patients":[410,446,762,817,1282,1496,1909,1926,1999,2069],"on":[411,468,824,1625,1944],"waiting":[413],"list":[414],"die":[415],"within":[416,677,811],"5":[417],"11.":[419],"As":[420,978,1964],"suggested":[421],"decades,":[423],"could":[425,695,719,854,1156,1207],"issue.":[431],"Now":[432],"question":[434],"is,":[435],"we":[437,1374,1680,1710],"ready":[438],"large-scale":[441,2040],"xenotransplant":[443,1483,1527,1618,1738],"trial":[444,872,1739],"disease?":[450],"While":[451,752,1202,1257,1842],"presents":[453],"many":[454,1195],"challenges,":[456],"physiological":[458,602],"discordance,":[459],"microbial":[460],"safety,":[461],"aspects,":[464],"our":[465,1727],"focus":[466,1624],"current":[470,827,1688],"surrounding":[472,1505],"rejection.2.":[474],"Human":[475],"studies":[477,629,650,691,1074,1614],"vs.":[480],"xenotransplantationThe":[482],"most":[483,761,791],"note-worthy":[484],"recent":[487,792],"efforts":[489,1163],"1,12,13.":[498],"61":[513],"Additionally,":[517,565,1389,1469],"option":[520,757],"or":[524,553,601,610,1328,1571,1636,1761,1809,1915],"surgical":[525,1653,1668],"therapy":[526,1510],"available":[528,1951,1962],"alternative":[534,1178],"care":[535],"would":[537,674,845,1695],"transition":[542,1596],"comfort":[544],"measures.":[545],"extension":[547],"their":[549],"lives":[550],"month":[552],"two,":[554],"longer":[559],"commendable":[563,1552],"effort.":[564],"evaluate":[567,1715,2044],"functionality":[569],"immunological":[571,1499],"response":[572,1323,1587],"xenokidney":[575,739,830,843,870,940,963,1851,2050],"context,":[579],"decedent":[581,717],"employed":[585],"2,3.":[586,612],"In":[587,1042,1091,1149,1708],"model,":[589],"deemed":[593],"ineligible":[594],"donation":[597],"due":[598,640,698,808,1099],"trauma":[600],"considerations,":[603],"utilized":[605,1781],"xenokidneys":[609],"xenohearts":[611],"organs":[614,1642],"monitored":[616],"signs":[618],"rejection":[620,810,1352,1456,1461,1579,1616,1914,2066],"function":[622],"encouraging":[624],"results":[625,728,794,894],"date.":[627],"These":[628],"provide":[630,2071],"reassurance":[631],"low":[634],"likelihood":[635],"immediate":[637],"hyperacute":[642,1578],"rejection.":[643],"worth":[647],"noting":[648],"involving":[651,671],"individuals":[653,673,694],"do":[654],"require":[656,1530,1650],"from":[658,663,687,716,1881],"FDA,":[660,682],"local":[664],"Institutional":[665],"Review":[666],"Boards":[667],"(IRBs).":[668],"Nevertheless,":[669,1024],"research":[670],"encompassed":[676],"Clinical":[678,1829],"Trial":[679],"Applications":[680],"akin":[683],"data":[685,1238,1444],"obtained":[686],"non-clinical":[688],"studies.":[689],"Secondly,":[690],"brain-death":[693],"suboptimal":[697],"injuries":[700],"vital":[702],"organs,":[703],"changes":[704],"hormones,":[706],"metabolism,":[707],"hemodynamics,":[708],"excessive":[710],"inflammation,etc.":[711],"14.":[712],"Therefore,":[713,858],"outcome":[715],"models":[718,1484,1619],"difficult":[721],"interpret":[723],"less":[725,1920],"informative":[726],"than":[727,1706,1921],"living":[733],"recipients.In":[734],"case":[736,1293],"transplantation,":[740,842],"comparison":[742],"must":[745,1594],"against":[747,900,1665],"alternative:":[750],"dialysis.":[751,838,857],"allotransplantation":[753,1095,1494,1784],"preferable":[756],"dialysis":[759,784,883],"associated":[764],"life,":[771],"decreased":[773],"financial":[774],"costs,":[775],"unknown":[778],"how":[779],"compare":[782],"respect":[786],"outcomes.":[788,1127],"Unfortunately,":[789,1128],"NHPs":[796],"possessing":[801],"proteins":[803,973],"show":[804],"loss":[807],"2-3":[812],"months":[813,1940],"Even":[815],"experiencing":[818],"poor":[820],"life":[823],"comparable":[834],"those":[836,1780],"unlike":[840],"precipitate":[848],"death":[850],"return":[855,881],"crucial":[862],"discuss":[864],"candidates":[867],"relative":[874],"risks":[875,1690],"following":[876],"rejection,":[878],"such":[879,1324,1383],"subsequent":[885],"allotransplantation.":[886,1388],"An":[887],"consideration":[889],"whether":[891,1401],"antibody":[896,1438],"development":[897],"sensitization":[899],"kidneys.":[902,924],"homology":[906],"MHC,":[912],"may":[914,1269,1331,1392,1819],"further":[915,1168,2079],"limit":[916],"patient\u2019s":[918,1302],"pool":[920],"allogeneic":[922],"This":[925,1004,1674,2039],"issue":[926],"represents":[927],"another":[928],"points":[931],"addressed":[935],"prior":[936],"trial.3.":[941],"Unresolved":[942],"xenotransplantation3.1.":[945],"Lack":[946,1087,1414],"homogeneous":[948],"pre-clinical":[951],"study:":[953],"Anand":[954],"et":[955],"al.":[956],"present":[957],"favorable":[958],"pig-to-NHP":[962,1570],"employing":[966],"under":[974,1846],"anti-CD154mAb":[975],"previously":[979],"emphasized,":[980],"longest":[982,1936],"study":[987,1309,2041],"close":[989],"years,":[992],"mean":[995],"time":[997],"241.2":[999],"days":[1000],"(Median,":[1001],"176":[1002],"days).":[1003],"achievement":[1005],"stands":[1006],"out":[1007,1048],"significantly":[1008],"when":[1009],"compared":[1010],"previous":[1012],"rates":[1016],"using":[1017],"background.":[1023],"imperative":[1027],"overlook":[1030],"attain":[1038],"long-term":[1039,1209,1769,1825],"survival.":[1041],"cited":[1044],"(6":[1047],"15":[1050],"animals)":[1051],"survive":[1057],"past":[1058],"months.":[1060],"consistent":[1062,1797,1824],"occurrence":[1063],"early":[1065,1455,1810,1912],"failures":[1067],"virtually":[1069],"all":[1070],"nonhuman":[1071,1904],"primate":[1072,1905],"matter":[1077],"concern,":[1079],"often":[1080],"without":[1081,1577],"clearly":[1082],"discernible":[1083],"pathophysiology":[1084],"15.":[1085,1239],"3.2.":[1086],"optimized":[1089],"immunosuppression:":[1090],"1970s,":[1093],"discovery":[1102],"implementation":[1104,1703],"powerful":[1107],"immunosuppressive":[1108,1119,1205],"agent":[1109],"cyclosporine.":[1111],"addition":[1113],"cyclosporine":[1115],"recipient\u2019s":[1118],"led":[1121,1160,1219,1987],"drawback":[1130],"any":[1132,1756],"overimmunosuppression":[1137],"immune":[1141,1316,1586],"system":[1142],"infections":[1146],"side-effects.":[1148],"recognition":[1152],"CD40/CD154":[1154],"blockade":[1155],"prolong":[1157,1165],"immunosuppression.":[1169],"To":[1170,1609],"point,":[1172],"myriad":[1174],"mechanisms":[1179],"tried":[1182],"xenotransplantation.":[1184,1724,1841],"Not":[1185],"surprisingly,":[1186],"implemented":[1188],"includes":[1191],"diverse":[1192],"potentially":[1196],"relevant":[1197,1349],"mechanisms,":[1198],"some":[1199,1908],"perhaps":[1200],"redundant.":[1201],"aggressive":[1204],"approach":[1206],"facilitate":[1208],"subset":[1214],"animals,":[1216],"concurrently":[1218],"high":[1222],"incidence":[1223],"infectious":[1225,1790],"complications":[1226,1916],"euthanasia":[1229],"directly":[1231],"reported":[1232,1880],"reflected":[1234],"highly":[1236],"censored":[1237],"One":[1240],"example":[1241],"profound":[1243],"repeated":[1247,1264],"rituximab":[1250],"control":[1252],"post-xenotransplantation":[1253],"humoral":[1254,1322],"responses":[1255],"9,16.":[1256],"excellent":[1259],"proof":[1260,1541],"concept":[1262,1543],"approach,":[1263],"depletion":[1265],"B":[1267],"cells":[1268],"lend":[1271],"itself":[1272],"safe":[1274,1721],"translation":[1276],"clinic.":[1279],"Overimmunosuppression":[1280],"puts":[1281],"at":[1283],"risk":[1284,1431,1500],"irreversible":[1286],"infection":[1287],"death,":[1289],"pertinent":[1290],"porcine":[1295],"CMV":[1296],"contributed":[1299],"demise":[1303],"Other":[1311],"more":[1314,1612,1697],"specific":[1315,1437],"cell":[1317],"populations":[1318],"involved":[1319],"proteasome":[1326],"inhibitors":[1327],"anti-CD38":[1329],"mAbs":[1330],"improve":[1332,1717],"efficacy.":[1333],"tested":[1340],"yet.":[1343,1963],"Several":[1344],"pathological":[1346],"features":[1347,1367,1391],"besides":[1353],"AMR,":[1354],"TMA":[1356],"interstitial":[1358],"hemorrhage.":[1359],"challenging":[1362],"determine":[1364,1473],"if":[1365],"truly":[1369],"\u201cspecific\u201d":[1370],"can":[1375,1574,1606],"observe":[1376],"injury":[1378],"patterns":[1379],"settings":[1382],"ABO":[1385],"mismatch":[1386],"occur":[1393],"secondary":[1394],"AMR.":[1396],"Consequently,":[1397],"unclear":[1400],"factors":[1403],"sufficient":[1406,1773],"reject":[1408],"independently":[1411],"AMR.3.3":[1413],"histocompatibility":[1416,1426,1491,1532,1645],"thresholds:":[1417],"Improvements":[1418],"allotransplant":[1421],"mirrored":[1423],"advancements":[1424],"testing":[1427],"assess":[1429],"immunologic":[1430,1689,1788],"monitor":[1433,1786],"de":[1434],"novo":[1435],"development.":[1439],"Cellular":[1440],"flow":[1441],"cytometry":[1442],"crossmatch":[1443],"generated":[1447],"studies,":[1450],"thresholds":[1452,1492],"correlated":[1453],"phenotypes":[1457],"(such":[1458],"antibody-mediated":[1460],"thrombotic":[1463],"microangiopathy)":[1464],"establishment.":[1468],"thorough":[1470],"investigations":[1471],"specificity":[1475],"preformed":[1478],"anti-pig":[1479],"antibodies":[1480],"across":[1481],"different":[1482],"reported.":[1488],"stratify":[1495],"according":[1497],"inform":[1502],"decision-making":[1504],"induction":[1509],"baseline":[1512],"levels.":[1514],"Establishing":[1515],"appropriate":[1516,1644],"recipient/pig-donor":[1517],"pairs":[1518],"conjunction":[1520],"regimens":[1524],"trials":[1528,1605,1975],"adequate":[1531],"tools":[1533],"thresholds.":[1535],"4.":[1536],"Constructive":[1537],"future":[1538],"directions":[1539,2076],"(from":[1540],"optimization":[1545,1599],"phase):":[1546],"achieved":[1551,1576],"utilization":[1556],"model.":[1560],"Studies":[1561],"date":[1563],"serve":[1564],"proof-of-concept,":[1567],"demonstrating":[1568],"providing":[1581],"insights":[1582],"xenograft.":[1590],"now":[1595,1950],"into":[1597,1982,2034],"phase":[1600],"before":[1601],"larger":[1602],"initiated.":[1608],"accomplish":[1610],"this,":[1611],"mechanism-driven":[1613],"imperative,":[1621],"investigating":[1626],"therapeutics":[1627],"target":[1629],"pathways":[1631],"combination":[1633],"new":[1635],"currently":[1637],"used":[1638],"testing.5.":[1646],"innovation":[1649,1669],"risk:A":[1651],"prominent":[1652],"educator":[1654],"20th":[1657],"century,":[1658],"Dr.":[1659],"David":[1660],"Sabiston,":[1661],"warned":[1662],"his":[1663],"trainees":[1664],"holding":[1666],"back":[1667],"making":[1671],"rash":[1672],"pronouncements.":[1673],"advice":[1675],"seems":[1676],"wise,":[1677],"while":[1679,1924,1956],"hold":[1681],"opinions":[1683],"expressed":[1684],"above":[1685],"one":[1694,1933],"delighted":[1698],"see":[1700],"us.":[1707],"fact,":[1709],"working":[1712],"hard":[1713],"permit":[1720],"humble":[1728],"suggestion":[1729],"group":[1732],"leads":[1734,1767],"following:":[1743],"rigorously":[1746],"defined":[1747],"genome":[1749],"information":[1751,1943],"off-target":[1753],"integration":[1754],"transgenes":[1757],"FDA-approved":[1760],"clinically":[1762],"acceptable":[1763],"routinely":[1766],"3)":[1772],"pre-":[1774],"post-xenotransplant":[1776],"assays":[1777],"replicate":[1779],"status":[1791],"4)":[1796],"preclinical":[1801],"mechanistic":[1805],"explanation":[1806],"outliers":[1808],"rejections.":[1811],"We":[1812],"expect":[1813],"progress":[1815],"open":[1820],"door":[1822],"xenografts.6.":[1828],"trials:It":[1834],"indeed":[1836],"exciting":[1838],"era":[1839],"manuscript":[1844,1866],"preparation":[1847],"review,":[1849],"transplantations":[1852],"approved":[1855,1972],"FDA":[1857,1970,2026],"(compassionate":[1858],"use)":[1859],"conducted":[1861],"during":[1862],"processing":[1864],"17-19.":[1867],"So":[1868],"far,":[1869],"total":[1871],"six":[1873],"2022":[1882],"2025,":[1884,1967],"average":[1887],"age":[1889],"56.8":[1891],"(four":[1893],"males":[1894],"females)":[1897],"(Table":[1898],"2).":[1899,2016],"Similar":[1900],"findings":[1902],"(NHP)":[1906],"models,":[1907],"(mean":[1917],"months),":[1923],"remain":[1927],"ongoing":[1928],"functioning":[1930],"graft,":[1931],"(~3":[1939],"post-transplantation).":[1941],"Detailed":[1942],"academic":[1953],"publications":[1954],"1,12,13":[1955],"latter":[1957],"February":[1966],"U.S.":[1969],"engineered":[1978],"humans.":[1983],"Massachusetts":[1989],"General":[1990],"Hospital":[1991],"(MGH)":[1992],"eGenesis,":[1994],"involves":[1995],"disease.":[2003],"initial":[2005],"series":[2009],"already":[2011],"initiated":[2012],"(Case#6":[2013],"Table":[2015],"sponsored":[2020],"Therapeutics,":[2023],"received":[2025],"kidneys":[2033],"50":[2037],"patients.":[2038],"aims":[2042],"safety":[2046],"efficacy":[2048],"shortage":[2058],"crisis.":[2059],"progression,":[2061],"timing,":[2062],"phenotype":[2064],"pursue":[2078],"advancements.":[2080]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":1}],"updated_date":"2026-09-26T08:19:03.415552","created_date":"2025-10-10T00:00:00"}