Prevention of Hyperacute Rejection in a Model of Orthotopic Liver Xenotransplantation From Pig to Baboon Using Polytransgenic Pig Livers (CD55, CD59, and H-Transferase)

Ramı́rez, Pablo; Montoya, M.J.; Rı́os, Antonio; Palenciano, C.G; Majado, Maria Juliana; Chávez, Rafael; Muñoz, Antonio; Fernández, Olga; Sánchez, Andrés; Segura, B.; Sansano, T; Acosta, F; Robles, R; Sánchez, Francisco; Fuente, Teodomiro; Cascales, Pedro; González, Francisco; Ruiz, Didye; Martínez, Laura; Pons, J.A.; Rodríguez, J.I.; Yélamos, José; Cowan, Peter J.; d’Apice, Anthony J.F.; Parrilla, Pascual

doi:10.1016/j.transproceed.2005.09.186

Cited by 72 publications

(56 citation statements)

References 13 publications

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“…In-vitro CD59 producing porcine cells strongly resist from the exposure of human complement and anti-porcine antibody [47], although ex vivo experimentation shows only partial protection in the case of porcine lungs perfused with human blood [49]. Technology has advanced so considerably now that polytransgenic pigs have also been produced [50]. Although livers transplanted from polytransgenic pigs for hDAF, CD59, and alfa 1,2-fucosyltransferase to baboons prevented HAR, xenografts still induced delayed rejection.…”

Section: Advances In Xenotransplantation Of Porcine Tissuesmentioning

confidence: 99%

Porcine Embryonic Stem Cells: A Possible Source for Cell Replacement Therapy

Hall

2008

Stem Cell Rev

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The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences in porcine pre-implantation development compared to the mouse and human. Expression of oct4, nanog and sox2 differs in the zona-enclosed porcine blastocyst compared to its mouse and human counterparts, which may suggest that other factors may be responsible for maintaining porcine pluripotency in the early blastocyst. In addition, the epiblast forms considerably later, at days 7 to 8 when the porcine blastocyst begins to hatch and is maintained for 4 days before completely differentiating. This review covers an outline of the known molecular profile during porcine pre-implantation development and provides a history in the development of putative pESCs to date. Greater knowledge on the molecular mechanisms that underlie porcine pluripotency and pre-implantation development may aid in improving the development of pESCs.

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Section: Advances In Xenotransplantation Of Porcine Tissuesmentioning

confidence: 99%

Porcine Embryonic Stem Cells: A Possible Source for Cell Replacement Therapy

Hall

2008

Stem Cell Rev

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“…(18) These polygenic pigs expressed h-DAF in addition to the human complement regulator protein CD59 and alfa 1,2-fucosyltransferase (H-transferase). (18) Although recipients of polygenic liver xenografts were noted to have absence of hyperacute rejection and preserved liver architecture on necropsy, survival was limited to between 13 and 24 hours with cause of death being thrombosis in three cases and primary xenograft dysfunction in one case. (18)…”

Section: Laboratory Experience With Liver Xenotransplantationmentioning

confidence: 99%

“…(18) Although recipients of polygenic liver xenografts were noted to have absence of hyperacute rejection and preserved liver architecture on necropsy, survival was limited to between 13 and 24 hours with cause of death being thrombosis in three cases and primary xenograft dysfunction in one case. (18)…”

Section: Laboratory Experience With Liver Xenotransplantationmentioning

confidence: 99%

Liver xenotransplantation

Patel¹,

Louras

Vagefi³

2017

Current Opinion in Organ Transplantation

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Purpose of Review There continues to be inadequate organ supply, and lack of effective temporary support, for patients with liver failure. The purpose of this review is to discuss recent progress in the field of orthotopic pig-to-nonhuman primate (NHP) liver xenotransplantation (LXT). Recent Findings From 1968 to 2012, survival in pig-to-NHP LXT has been limited to 9 days, initially due to hyperacute rejection which has been ameliorated through use of genetically engineered donor organs, but ultimately due to profound thrombocytopenia, thrombotic microangiopathy (TMA), and bleeding. More recently, demise secondary to lethal coagulopathy was avoided with LXT of α(1,3)-galactosyltransferase (GT) knockout (GTKO), CMV-negative porcine xenografts into baboons receiving exogenous administration of coagulation factors and co-stimulation blockade, establishing that a porcine liver is capable of supporting NHP life for nearly a month. Summary Continued consistent achievement of pig-to-NHP LXT survival beyond two weeks justifies consideration of a clinical application as a bridge to allotransplantation for patients with acute hepatic failure. Further genetic modifications to the donor, as well as additional studies, are required in order to apply LXT as destination therapy.

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“…13–15 In a subsequent brief report by this group, livers from pigs transgenic for 2 hRCAs (CD55, CD59) and H-transferase survived only 13–24 hours in baboons. 16 …”

Section: Introductionmentioning

confidence: 99%

Pig Liver Xenotransplantation

et al. 2016

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Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained. Other topics discussed include the possible mechanisms for the development of the thrombocytopenis that rapidly occurs after pig liver xenotransplantation in a primate, the impact of pig complement on graft injury, the potential infectious risks, and potential physiologic incompatibilities between pig and human. There is cautious optimism that all of these problems can be overcome by judicious genetic manipulation of the pig. If liver graft survival could be achieved in the absence of thrombocytopenia or rejection for a period of even a few days, there may be a role for pig liver transplantation as a bridge to allotransplantation in carefully selected patients.

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Prevention of Hyperacute Rejection in a Model of Orthotopic Liver Xenotransplantation From Pig to Baboon Using Polytransgenic Pig Livers (CD55, CD59, and H-Transferase)

Cited by 72 publications

References 13 publications

Porcine Embryonic Stem Cells: A Possible Source for Cell Replacement Therapy

Porcine Embryonic Stem Cells: A Possible Source for Cell Replacement Therapy

Liver xenotransplantation

Pig Liver Xenotransplantation

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