Correction of acute liver cell failure disorders through liver xenoperfusion: Experimental study

Adham, Mustapha; Sab, J. M.; Ducerf, C.; Tassaux, Didier; Vianey‐Saban, Christine; Chevallier, M.; Le, Qi; Bizollon, T.; Barakat, C; Debize, G; Vernet, M.; Pouyet, M; Baulieux, J.

doi:10.1016/s0041-1345(97)00764-1

Cited by 7 publications

(7 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following pig-to-human ex vivo liver perfusion for 19h, Adham et al studied PT and some coagulation factors, such as FV, FVII, FIX, FX, and FXII (33). Their data showed some benefit to the patient in total bilirubin levels, but they did not observe correction of coagulation.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Function After Genetically Engineered Pig Liver Transplantation in Baboons

et al. 2010

View full text Add to dashboard Cite

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatic Function After Genetically Engineered Pig Liver Transplantation in Baboons

et al. 2010

View full text Add to dashboard Cite

show abstract

“…However, decreased levels of vitamin K-dependent clotting factors (VII and X) were documented to be produced by the pig liver [79][80][81]. There is also some evidence that pig hepatocytes can remove bilirubin from human blood [80,82]. Although unlikely, there is also a risk that pig hepatocytes will phagocytose human erythrocytes [83][84][85][86][87] and/or platelets [85,[88][89][90][91][92]; it is unlikely this will occur in the absence of vascular endothelial cells and Kupffer cells.…”

Section: Resultsmentioning

confidence: 99%

Experimental hepatocyte xenotransplantation—a comprehensive review of the literature

Zhou

Liu

Ezzelarab

et al. 2015

Xenotransplantation

View full text Add to dashboard Cite

Background Hepatocyte transplantation is a potential therapy for certain diseases of the liver, including hepatic failure. However, there is a limited supply of human livers as a source of cells and, after isolation, human hepatocytes can be difficult to expand in culture, limiting the number available for transplantation. Hepatocytes from other species, e.g., the pig, have therefore emerged as a potential alternative source. We searched the literature through the end of 2014 to assess the current status of experimental research into hepatocyte xenotransplantation. Literature search and results The literature search identified 51 reports of in vivo cross-species transplantation of hepatocytes in a variety of experimental models. Most studies investigated the transplantation of human (n=23) or pig (n=19) hepatocytes. No studies explored hepatocytes from genetically-engineered pigs. The spleen was the most common site of transplantation (n=23), followed by the liver (through the portal vein [n=6]) and peritoneal cavity (n=19). In 47 studies (92%), there was evidence of hepatocyte engraftment and function across a species barrier. Conclusions The data provided by this literature search strengthen the hypothesis that xenotransplantation of hepatocytes is feasible and potentially successful as a clinical therapy for certain liver diseases, including hepatic failure. By excluding vascular structures, hepatocytes isolated from genetically-engineered pig livers may address some of the immunological problems of xenotransplantation.

show abstract

“…150,151 However, hyperacute rejection is not a major obstacle for biologic support of ALF patients because of their very low complement level and the availability of transgenic pigs. 107,110,111 Beside the currently known zoonosis, another main obstacle is the risk of transmitting a porcine virus or other unknown pathogens from the pig to humans. To control these risks, a specific germ free breeding needs to be developed, and the possibility of viral material transmission needs to be evaluated, in particular the porcine retrovirus.…”

Section: Discussionmentioning

confidence: 99%

“…108,109 Because FH patients have a very low complement level, clinical and experimental data tend to show that xenogenic liver perfusion is associated with minimal or no hyperacute rejection, providing that patients do not receive blood or blood derivative immediately before or during xenoperfusion. 110,111 The clinical application of porcine ECLP was also subjected to the same physiologic, immunologic, and virologic restrictions of the xenograft.…”

Section: Extracorporeal Whole Liver Perfusionmentioning

confidence: 99%

Extracorporeal Liver Support: Waiting for the Deciding Vote

Adham

2003

ASAIO Journal

View full text Add to dashboard Cite

Because acute liver cell failure is associated with an exceedingly high mortality, liver support has been proposed since the 1950s to improve patient outcome. Early devices, including hemodialysis, hemofiltration, exchange transfusion, plasmapheresis, hemoperfusion, plasma and cross-hemodialysis or cross-circulation, appeared inefficient. Meanwhile, documented results of extracorporeal liver perfusion (ECLP) suggested its superiority over conventional treatment. These devices were abandoned with the development of liver transplantation (LT), which allowed a better outcome and longer survival rate. In the present day, the fact that patients die while waiting for LT because of organ shortage led to a renewed interest in liver support as bridge to LT or regeneration. These devices can be classified according to the presence or lack of hepatocytes, whereas biologic devices refers to the presence of cells or other organic and biochemical component. The absence of individual success of early models led to the development of combined hepatocyte free devices, or artificial liver, which are based upon the hemodiabsorption principle (Biologic-DT) or on the "albumin bound toxin hypothesis" (Molecular Adsorbents Recirculating System) with encouraging results. Meanwhile, hepatocyte based bioartificial liver devices (BLD) were conceived for a global "metabolic support." BLD were developed with the use of human hepatoma cell line (C3A) or primary or cryopreserved porcine hepatocytes. Preliminary experience gave promising results bridging patients to LT. Based upon the same principle of global hepatocyte metabolic support, ECLP regained interest, particularly with the development of transgenic pigs. Several concerns were raised about these devices. Artificial livers lacked any metabolic synthetic activity, the use of human liver for ECLP seems hardly acceptable because of organ shortage, and the accepted use of borderline livers for transplantation is pending trials for the use of xenogenic livers. For BLD, the concerns were the low hepatocyte mass, the absence of accessory liver cells, and the potential risk of seeding tumor cells into patient with the use of human hepatoma cell line. The use of porcine hepatocytes (BLD or ECLP) raised physiologic and immunologic concerns and particularly the fear of a possible transfer of porcine viral material. Although recent studies clearly demonstrate clinical improvement of patients with the use of recently developed liver support devices, most of reported prospective, controlled, or randomized trials had a small number of patients. To give the deciding vote and avoid previous pitfalls, trials need to be developed with a larger number of patients based upon statistically significant models with the following characteristics: 1) comprehensive understanding of the acute liver cell failure mechanisms, 2) world wide classification of conditions that require liver support, and 3) a clear definition of treatment success pending patients to LT or recovery without transplantation. There has not y...

show abstract

Correction of acute liver cell failure disorders through liver xenoperfusion: Experimental study

Cited by 7 publications

References 4 publications

Hepatic Function After Genetically Engineered Pig Liver Transplantation in Baboons

Hepatic Function After Genetically Engineered Pig Liver Transplantation in Baboons

Experimental hepatocyte xenotransplantation—a comprehensive review of the literature

Extracorporeal Liver Support: Waiting for the Deciding Vote

Contact Info

Product

Resources

About