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A non-human primate model of acute liver failure suitable for testing liver support systems

Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that l...

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Autores principales: Kalsi, Ranjeet S., Ostrowska, Alina, Olson, Adam, Quader, Mubina, Deutsch, Melvin, Arbujas-Silva, Norma J., Symmonds, Jen, Soto-Gutierrez, Alejandro, Crowley, John J., Reyes-Mugica, Miguel, Sanchez-Guerrero, Giselle, Jaeschke, Hartmut, Amiot, Bruce P., Cascalho, Marilia, Nyberg, Scott L., Platt, Jeffrey L., Tafaleng, Edgar N., Fox, Ira J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561471/
https://www.ncbi.nlm.nih.gov/pubmed/36250086
http://dx.doi.org/10.3389/fmed.2022.964448
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author Kalsi, Ranjeet S.
Ostrowska, Alina
Olson, Adam
Quader, Mubina
Deutsch, Melvin
Arbujas-Silva, Norma J.
Symmonds, Jen
Soto-Gutierrez, Alejandro
Crowley, John J.
Reyes-Mugica, Miguel
Sanchez-Guerrero, Giselle
Jaeschke, Hartmut
Amiot, Bruce P.
Cascalho, Marilia
Nyberg, Scott L.
Platt, Jeffrey L.
Tafaleng, Edgar N.
Fox, Ira J.
author_facet Kalsi, Ranjeet S.
Ostrowska, Alina
Olson, Adam
Quader, Mubina
Deutsch, Melvin
Arbujas-Silva, Norma J.
Symmonds, Jen
Soto-Gutierrez, Alejandro
Crowley, John J.
Reyes-Mugica, Miguel
Sanchez-Guerrero, Giselle
Jaeschke, Hartmut
Amiot, Bruce P.
Cascalho, Marilia
Nyberg, Scott L.
Platt, Jeffrey L.
Tafaleng, Edgar N.
Fox, Ira J.
author_sort Kalsi, Ranjeet S.
collection PubMed
description Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy.
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spelling pubmed-95614712022-10-15 A non-human primate model of acute liver failure suitable for testing liver support systems Kalsi, Ranjeet S. Ostrowska, Alina Olson, Adam Quader, Mubina Deutsch, Melvin Arbujas-Silva, Norma J. Symmonds, Jen Soto-Gutierrez, Alejandro Crowley, John J. Reyes-Mugica, Miguel Sanchez-Guerrero, Giselle Jaeschke, Hartmut Amiot, Bruce P. Cascalho, Marilia Nyberg, Scott L. Platt, Jeffrey L. Tafaleng, Edgar N. Fox, Ira J. Front Med (Lausanne) Medicine Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy. Frontiers Media S.A. 2022-09-30 /pmc/articles/PMC9561471/ /pubmed/36250086 http://dx.doi.org/10.3389/fmed.2022.964448 Text en Copyright © 2022 Kalsi, Ostrowska, Olson, Quader, Deutsch, Arbujas-Silva, Symmonds, Soto-Gutierrez, Crowley, Reyes-Mugica, Sanchez-Guerrero, Jaeschke, Amiot, Cascalho, Nyberg, Platt, Tafaleng and Fox. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Kalsi, Ranjeet S.
Ostrowska, Alina
Olson, Adam
Quader, Mubina
Deutsch, Melvin
Arbujas-Silva, Norma J.
Symmonds, Jen
Soto-Gutierrez, Alejandro
Crowley, John J.
Reyes-Mugica, Miguel
Sanchez-Guerrero, Giselle
Jaeschke, Hartmut
Amiot, Bruce P.
Cascalho, Marilia
Nyberg, Scott L.
Platt, Jeffrey L.
Tafaleng, Edgar N.
Fox, Ira J.
A non-human primate model of acute liver failure suitable for testing liver support systems
title A non-human primate model of acute liver failure suitable for testing liver support systems
title_full A non-human primate model of acute liver failure suitable for testing liver support systems
title_fullStr A non-human primate model of acute liver failure suitable for testing liver support systems
title_full_unstemmed A non-human primate model of acute liver failure suitable for testing liver support systems
title_short A non-human primate model of acute liver failure suitable for testing liver support systems
title_sort non-human primate model of acute liver failure suitable for testing liver support systems
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561471/
https://www.ncbi.nlm.nih.gov/pubmed/36250086
http://dx.doi.org/10.3389/fmed.2022.964448
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