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Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model

The liver’s regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine...

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Autores principales: Navarro-Alvarez, Nalu, Machaidze, Zurab, Schuetz, Christian, Zhu, Alexander, Liu, Wei-hui, Shah, Jigesh A., Vagefi, Parsia A., Elias, Nahel, Buhler, Leo, Sachs, David H., Markmann, James F., Yeh, Heidi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248961/
https://www.ncbi.nlm.nih.gov/pubmed/30462716
http://dx.doi.org/10.1371/journal.pone.0207272
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author Navarro-Alvarez, Nalu
Machaidze, Zurab
Schuetz, Christian
Zhu, Alexander
Liu, Wei-hui
Shah, Jigesh A.
Vagefi, Parsia A.
Elias, Nahel
Buhler, Leo
Sachs, David H.
Markmann, James F.
Yeh, Heidi
author_facet Navarro-Alvarez, Nalu
Machaidze, Zurab
Schuetz, Christian
Zhu, Alexander
Liu, Wei-hui
Shah, Jigesh A.
Vagefi, Parsia A.
Elias, Nahel
Buhler, Leo
Sachs, David H.
Markmann, James F.
Yeh, Heidi
author_sort Navarro-Alvarez, Nalu
collection PubMed
description The liver’s regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine in a baboon model of Post-Hepatectomy Liver Failure (PHLF) by 90%- hepatectomy. Immunosuppression consisted of CVF, ATG, FK 506 and steroids. 90%-hepatectomized animals died within 4–5 days with the clinical picture of PHLF, (high LFTs and bilirubin, ascites, encephalopathy and coagulopathy). The 10% remnants had macroscopic and histological evidence of severe steatosis and absence of hepatocyte replication. In contrast, the addition of XHALT prolonged survival up to 11 days, with the cause of death being sepsis, rather than liver failure. The remnant liver appeared grossly normal, and on histology, there was no evidence of fatty infiltration, but there was pronounced Ki-67 staining. In conclusion, temporary auxiliary xenografts have the potential to support a small for size liver graft while it grows to adequate size or provide an opportunity for organ recovery in acute liver failure.
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spelling pubmed-62489612018-12-06 Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model Navarro-Alvarez, Nalu Machaidze, Zurab Schuetz, Christian Zhu, Alexander Liu, Wei-hui Shah, Jigesh A. Vagefi, Parsia A. Elias, Nahel Buhler, Leo Sachs, David H. Markmann, James F. Yeh, Heidi PLoS One Research Article The liver’s regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine in a baboon model of Post-Hepatectomy Liver Failure (PHLF) by 90%- hepatectomy. Immunosuppression consisted of CVF, ATG, FK 506 and steroids. 90%-hepatectomized animals died within 4–5 days with the clinical picture of PHLF, (high LFTs and bilirubin, ascites, encephalopathy and coagulopathy). The 10% remnants had macroscopic and histological evidence of severe steatosis and absence of hepatocyte replication. In contrast, the addition of XHALT prolonged survival up to 11 days, with the cause of death being sepsis, rather than liver failure. The remnant liver appeared grossly normal, and on histology, there was no evidence of fatty infiltration, but there was pronounced Ki-67 staining. In conclusion, temporary auxiliary xenografts have the potential to support a small for size liver graft while it grows to adequate size or provide an opportunity for organ recovery in acute liver failure. Public Library of Science 2018-11-21 /pmc/articles/PMC6248961/ /pubmed/30462716 http://dx.doi.org/10.1371/journal.pone.0207272 Text en © 2018 Navarro-Alvarez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Navarro-Alvarez, Nalu
Machaidze, Zurab
Schuetz, Christian
Zhu, Alexander
Liu, Wei-hui
Shah, Jigesh A.
Vagefi, Parsia A.
Elias, Nahel
Buhler, Leo
Sachs, David H.
Markmann, James F.
Yeh, Heidi
Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
title Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
title_full Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
title_fullStr Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
title_full_unstemmed Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
title_short Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
title_sort xenogeneic heterotopic auxiliary liver transplantation (xhalt) promotes native liver regeneration in a post-hepatectomy liver failure model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248961/
https://www.ncbi.nlm.nih.gov/pubmed/30462716
http://dx.doi.org/10.1371/journal.pone.0207272
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