Design and testing of a humanized porcine donor for xenotransplantation.

التفاصيل البيبلوغرافية
العنوان:	Design and testing of a humanized porcine donor for xenotransplantation.
المؤلفون:	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.; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Paragas VB; eGenesis, Cambridge, MA, USA., Akkad A; eGenesis, Cambridge, MA, USA., Chhangawala S; eGenesis, Cambridge, MA, USA., Colvin RB; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Ernst RJ; eGenesis, Cambridge, 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; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Li F; eGenesis, Cambridge, MA, USA., Low SC; eGenesis, Cambridge, MA, USA., Matheson R; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Nehring C; eGenesis, Cambridge, MA, USA., Otsuka R; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Pandelakis M; eGenesis, Cambridge, MA, USA., Policastro RA; eGenesis, Cambridge, MA, USA., Pols R; eGenesis, Cambridge, MA, USA., Queiroz L; eGenesis, Cambridge, MA, USA., Rosales IA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Serkin WT; eGenesis, Cambridge, MA, USA., Stiede K; eGenesis, Cambridge, MA, USA., Tomosugi T; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Xue Y; eGenesis, Cambridge, 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; Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, USA., Aufhauser D; Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA., Capuano S; Wisconsin National Primate Research Center, Madison, WI, USA., Kaufman DB; Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA., Knechtle SJ; Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, USA., Kwun J; Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, USA., Shanmuganayagam D; Department of Animal and Dairy Science, University of Wisconsin, Madison, WI, USA., Markmann JF; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Church GM; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Wyss Institute of Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA., Curtis M; eGenesis, Cambridge, MA, USA., Kawai T; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Youd ME; eGenesis, Cambridge, MA, USA. michele.youd@egenesisbio.com., Qin W; eGenesis, Cambridge, MA, USA. wenning.qin@egenesisbio.com.
المصدر:	Nature [Nature] 2023 Oct; Vol. 622 (7982), pp. 393-401. Date of Electronic Publication: 2023 Oct 11.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة:	Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH:	Graft Rejection/immunology , Graft Rejection/prevention & control , Kidney Transplantation/methods , Macaca fascicularis , Swine/genetics , Transplantation, Heterologous/methods, Animals ; Humans ; Animals, Genetically Modified ; Endothelial Cells/immunology ; Endothelial Cells/metabolism ; Polysaccharides/deficiency ; Transgenes/genetics
مستخلص:	Recent human decedent model studies ^1,2 and compassionate xenograft use ³ 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. (© 2023. The Author(s).)
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معلومات مُعتمدة:	P51 OD011106 United States OD NIH HHS; T32 AI007529 United States AI NIAID NIH HHS
المشرفين على المادة:	0 (Polysaccharides)
تواريخ الأحداث:	Date Created: 20231011 Date Completed: 20231025 Latest Revision: 20240210
رمز التحديث:	20240210
مُعرف محوري في PubMed:	PMC10567564
DOI:	10.1038/s41586-023-06594-4
PMID:	37821590
قاعدة البيانات:	MEDLINE

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تدمد:	1476-4687
DOI:	10.1038/s41586-023-06594-4