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Design and testing of a humanized porcine donor for xenotransplantation.
Anand, Ranjith P; Layer, Jacob V; Heja, David; Hirose, Takayuki; Lassiter, Grace; Firl, Daniel J; Paragas, Violette B; Akkad, Adam; Chhangawala, Sagar; Colvin, Robert B; Ernst, Russell J; Esch, Nicholas; Getchell, Kristen; Griffin, Alexandra K; Guo, Xiaoyun; Hall, Katherine C; Hamilton, Paula; Kalekar, Lokesh A; Kan, Yinan; Karadagi, Ahmad; Li, Feng; Low, Susan C; Matheson, Rudy; Nehring, Claudia; Otsuka, Ryo; Pandelakis, Matthew; Policastro, Robert A; Pols, Rebecca; Queiroz, Luis; Rosales, Ivy A; Serkin, William T; Stiede, Kathryn; Tomosugi, Toshihide; Xue, Yongqiang; Zentner, Gabriel E; Angeles-Albores, David; Chris Chao, J; Crabtree, Juliet N; Harken, Sierra; Hinkle, Nicole; Lemos, Tania; Li, Mailin; Pantano, Lorena; Stevens, Denise; Subedar, Omar D; Tan, Xiaoqing; Yin, Shiyi; Anwar, Imran J; Aufhauser, David; Capuano, Saverio.
Afiliação
  • Anand RP; eGenesis, Cambridge, MA, USA.
  • Layer JV; eGenesis, Cambridge, MA, USA.
  • Heja D; eGenesis, Cambridge, MA, USA.
  • Hirose T; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Lassiter G; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Firl DJ; eGenesis, Cambridge, MA, USA.
  • Paragas VB; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Akkad A; eGenesis, Cambridge, MA, USA.
  • Chhangawala S; eGenesis, Cambridge, MA, USA.
  • Colvin RB; eGenesis, Cambridge, MA, USA.
  • Ernst RJ; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Esch N; eGenesis, Cambridge, MA, USA.
  • Getchell K; eGenesis, Cambridge, MA, USA.
  • Griffin AK; eGenesis, Cambridge, MA, USA.
  • Guo X; eGenesis, Cambridge, MA, USA.
  • Hall KC; eGenesis, Cambridge, MA, USA.
  • Hamilton P; eGenesis, Cambridge, MA, USA.
  • Kalekar LA; eGenesis, Cambridge, MA, USA.
  • Kan Y; eGenesis, Cambridge, MA, USA.
  • Karadagi A; eGenesis, Cambridge, MA, USA.
  • Li F; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Low SC; eGenesis, Cambridge, MA, USA.
  • Matheson R; eGenesis, Cambridge, MA, USA.
  • Nehring C; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Otsuka R; eGenesis, Cambridge, MA, USA.
  • Pandelakis M; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Policastro RA; eGenesis, Cambridge, MA, USA.
  • Pols R; eGenesis, Cambridge, MA, USA.
  • Queiroz L; eGenesis, Cambridge, MA, USA.
  • Rosales IA; eGenesis, Cambridge, MA, USA.
  • Serkin WT; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Stiede K; eGenesis, Cambridge, MA, USA.
  • Tomosugi T; eGenesis, Cambridge, MA, USA.
  • Xue Y; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Zentner GE; eGenesis, Cambridge, MA, USA.
  • Angeles-Albores D; eGenesis, Cambridge, MA, USA.
  • Chris Chao J; eGenesis, Cambridge, MA, USA.
  • Crabtree JN; eGenesis, Cambridge, MA, USA.
  • Harken S; eGenesis, Cambridge, MA, USA.
  • Hinkle N; eGenesis, Cambridge, MA, USA.
  • Lemos T; eGenesis, Cambridge, MA, USA.
  • Li M; eGenesis, Cambridge, MA, USA.
  • Pantano L; eGenesis, Cambridge, MA, USA.
  • Stevens D; eGenesis, Cambridge, MA, USA.
  • Subedar OD; eGenesis, Cambridge, MA, USA.
  • Tan X; eGenesis, Cambridge, MA, USA.
  • Yin S; eGenesis, Cambridge, MA, USA.
  • Anwar IJ; eGenesis, Cambridge, MA, USA.
  • Aufhauser D; Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
  • Capuano S; Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Nature ; 622(7982): 393-401, 2023 Oct.
Article em En | MEDLINE | ID: mdl-37821590
Recent human decedent model studies1,2 and compassionate xenograft use3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The porcine donor was engineered to carry 69 genomic edits, eliminating glycan antigens, overexpressing human transgenes and inactivating porcine endogenous retroviruses. In vitro functional analyses showed that the edited kidney endothelial cells modulated inflammation to an extent that was indistinguishable from that of human endothelial cells, suggesting that these edited cells acquired a high level of human immune compatibility. When transplanted into cynomolgus monkeys, the kidneys with three glycan antigen knockouts alone experienced poor graft survival, whereas those with glycan antigen knockouts and human transgene expression demonstrated significantly longer survival time, suggesting the benefit of human transgene expression in vivo. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Suínos / Transplante Heterólogo / Transplante de Rim / Rejeição de Enxerto / Macaca fascicularis Limite: Animals / Humans Idioma: En Revista: Nature Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Suínos / Transplante Heterólogo / Transplante de Rim / Rejeição de Enxerto / Macaca fascicularis Limite: Animals / Humans Idioma: En Revista: Nature Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos