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Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present...

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Autores principales: Nelson, Victoria L., Stumbras, Aron R., Palumbo, R. Noelle, Riesgraf, Shawn A., Balboa, Marie S., Hannah, Zachary A., Bergstrom, Isaac J., Fecteau, Christopher J., Lake, John R., Barry, John J., Ross, Jeff J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604724/
https://www.ncbi.nlm.nih.gov/pubmed/37892931
http://dx.doi.org/10.3390/bioengineering10101201
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author Nelson, Victoria L.
Stumbras, Aron R.
Palumbo, R. Noelle
Riesgraf, Shawn A.
Balboa, Marie S.
Hannah, Zachary A.
Bergstrom, Isaac J.
Fecteau, Christopher J.
Lake, John R.
Barry, John J.
Ross, Jeff J.
author_facet Nelson, Victoria L.
Stumbras, Aron R.
Palumbo, R. Noelle
Riesgraf, Shawn A.
Balboa, Marie S.
Hannah, Zachary A.
Bergstrom, Isaac J.
Fecteau, Christopher J.
Lake, John R.
Barry, John J.
Ross, Jeff J.
author_sort Nelson, Victoria L.
collection PubMed
description Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.
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spelling pubmed-106047242023-10-28 Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure Nelson, Victoria L. Stumbras, Aron R. Palumbo, R. Noelle Riesgraf, Shawn A. Balboa, Marie S. Hannah, Zachary A. Bergstrom, Isaac J. Fecteau, Christopher J. Lake, John R. Barry, John J. Ross, Jeff J. Bioengineering (Basel) Article Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF. MDPI 2023-10-16 /pmc/articles/PMC10604724/ /pubmed/37892931 http://dx.doi.org/10.3390/bioengineering10101201 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nelson, Victoria L.
Stumbras, Aron R.
Palumbo, R. Noelle
Riesgraf, Shawn A.
Balboa, Marie S.
Hannah, Zachary A.
Bergstrom, Isaac J.
Fecteau, Christopher J.
Lake, John R.
Barry, John J.
Ross, Jeff J.
Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure
title Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure
title_full Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure
title_fullStr Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure
title_full_unstemmed Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure
title_short Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure
title_sort manufacturing and functional characterization of bioengineered liver grafts for extracorporeal liver assistance in acute liver failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604724/
https://www.ncbi.nlm.nih.gov/pubmed/37892931
http://dx.doi.org/10.3390/bioengineering10101201
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