Pig-to-Baboon Liver Xenografts

Calne, R. Y.; White, H. J. O.; Herbertson, B. M.; Millard, P. R.; Davis, D. R.; Salaman, J. R.; Samuel, Joshua

doi:10.1016/s0140-6736(68)91869-2

Cited by 83 publications

(32 citation statements)

References 7 publications

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“…Transplantation of porcine renal and cardiac xenografts in primates usually results in hyperacute rejection. On the other hand, this does not occur when a normal pig liver is transplanted into a primate [96]. The liver is perhaps less susceptible to complement mediated injury.…”

Section: Potential Of Xenogeneic Cell Transplantationmentioning

confidence: 97%

Strategies for liver support: from stem cells to xenotransplantation

Burra

Samuel

Wendon

et al. 2004

Journal of Hepatology

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Section: Potential Of Xenogeneic Cell Transplantationmentioning

confidence: 97%

Strategies for liver support: from stem cells to xenotransplantation

Burra

Samuel

Wendon

et al. 2004

Journal of Hepatology

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Section: Laboratory Experience With Liver Xenotransplantationmentioning

confidence: 99%

“…(11) In this pioneering study by Calne et al, seven pig-to-baboon orthotopic liver xenotransplants were performed with survival up to 3.5 days. (11) The longest surviving animal in this initial series received steroids and azathioprine for immunosuppression and died from bronchopneumonia with necropsy notable for preserved hepatocytes and evidence of mononuclear cell infiltration of the portal tracts. (11) Subsequent attempts two years later using rhesus monkey and chimpanzee as recipients were less successful and notable for recipient death in less than 12 hours with evidence of diffuse intravascular coagulation.…”

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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“…First studies in experimental preclinical pig-to-nonhuman primate liver xenotransplantation were performed by Calne et al in 1968 [6] using livers from unmodified (wild-type, WT) pigs. The status of WT pig liver xenotransplantation was discussed elsewhere [7][8][9].…”

Section: Progress With Genetically-engineered Pigsmentioning

confidence: 99%

Current status of pig liver xenotransplantation

Ekser

Markmann

Tector

2015

International Journal of Surgery

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The shortage of organs from deceased human donors is a major problem limiting the number of organs transplanted each year and results in the death of thousands of patients on the waiting list. Pigs are currently the preferred species for clinical organ xenotransplantation. Progress in genetically-engineered (GE) pig liver xenotransplantation increased graft and recipient survival from hours with unmodified pig livers to up to 9 days with normal to near-normal liver function. Deletion of genes such as GGTA1 (Gal-knockout pigs) or adding genes such as human complement regulatory proteins (hCD55, hCD46 expressing pigs) enabled hyperacute rejection to be overcome. Although survival up to 9 days was recorded, extended pig graft survival was not achieved due to lethal thrombocytopenia. The current status of GE pig liver xenotransplantation with world experience, potential factors causing thrombocytopenia, new targets on pig endothelial cells, and novel GE pigs with more genes deletion to avoid remaining antibody response, such as beta1,4-N-acetyl galactosaminyl transferase 2 (β4GalNT2), are discussed.

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Pig-to-Baboon Liver Xenografts

Cited by 83 publications

References 7 publications

Strategies for liver support: from stem cells to xenotransplantation

Strategies for liver support: from stem cells to xenotransplantation

Liver xenotransplantation

Current status of pig liver xenotransplantation

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