Kidney transplantation from triple-knockout pigs expressing multiple human proteins in cynomolgus macaques.

Autor: Ma D; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Hirose T; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Lassiter G; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sasaki H; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Rosales I; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Coe TM; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Rickert CG; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Matheson R; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Colvin RB; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Qin W; eGenesis Inc., Cambridge, Massachusetts, USA., Kan Y; eGenesis Inc., Cambridge, Massachusetts, USA., Layer JV; eGenesis Inc., Cambridge, Massachusetts, USA., Paragas VB; eGenesis Inc., Cambridge, Massachusetts, USA., Stiede K; eGenesis Inc., Cambridge, Massachusetts, USA., Hall KC; eGenesis Inc., Cambridge, Massachusetts, USA., Youd ME; eGenesis Inc., Cambridge, Massachusetts, USA., Queiroz LM; eGenesis Inc., Cambridge, Massachusetts, USA., Westlin WF; eGenesis Inc., Cambridge, Massachusetts, USA., Curtis M; eGenesis Inc., Cambridge, Massachusetts, USA., Yang L; eGenesis Inc., Cambridge, Massachusetts, USA., Markmann JF; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; eGenesis Inc., Cambridge, Massachusetts, USA., Kawai T; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Jan; Vol. 22 (1), pp. 46-57. Date of Electronic Publication: 2021 Aug 31.
DOI: 10.1111/ajt.16780
Abstrakt: Porcine cells devoid of three major carbohydrate xenoantigens, αGal, Neu5GC, and SDa (TKO) exhibit markedly reduced binding of human natural antibodies. Therefore, it is anticipated that TKO pigs will be better donors for human xenotransplantation. However, previous studies on TKO pigs using old world monkeys (OWMs) have been disappointing because of higher anti-TKO pig antibodies in OWMs than humans. Here, we show that long-term survival of renal xenografts from TKO pigs that express additional human transgenes (hTGs) can be achieved in cynomolgus monkeys. Kidney xenografts from TKO-hTG pigs were transplanted into eight cynomolgus recipients without pre-screening for low anti-pig antibody titers. Two recipients of TKO-hTG xenografts with low expression of human complement regulatory proteins (CRPs) (TKO-A) survived for 2 and 61 days, whereas six recipients of TKO-hTG xenografts with high CRP expression (TKO-B) survived for 15, 20, 71, 135, 265, and 316 days. Prolonged CD4 + T cell depletion and low anti-pig antibody titers, which were previously reported important for long-term survival of αGal knock-out (GTKO) xenografts, were not always required for long-term survival of TKO-hTG renal xenografts. This study indicates that OWMs such as cynomolgus monkeys can be used as a relevant model for clinical application of xenotransplantation using TKO pigs.
(© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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