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Cell release during perfusion reflects cold ischemic injury in rat livers

The global shortage of donor organs has made it crucial to deeply understand and better predict donor liver viability. However, biomarkers that effectively assess viability of marginal grafts for organ transplantation are currently lacking. Here, we showed that hepatocytes, sinusoidal endothelial, s...

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Autores principales: de Vries, Reinier J., Pendexter, Casie A., Cronin, Stephanie E. J., Marques, Beatriz, Hafiz, Ehab O. A., Muzikansky, Alona, van Gulik, Thomas M., Markmann, James F., Stott, Shannon L., Yeh, Heidi, Toner, Mehmet, Uygun, Korkut, Tessier, Shannon N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981218/
https://www.ncbi.nlm.nih.gov/pubmed/31980677
http://dx.doi.org/10.1038/s41598-020-57589-4
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author de Vries, Reinier J.
Pendexter, Casie A.
Cronin, Stephanie E. J.
Marques, Beatriz
Hafiz, Ehab O. A.
Muzikansky, Alona
van Gulik, Thomas M.
Markmann, James F.
Stott, Shannon L.
Yeh, Heidi
Toner, Mehmet
Uygun, Korkut
Tessier, Shannon N.
author_facet de Vries, Reinier J.
Pendexter, Casie A.
Cronin, Stephanie E. J.
Marques, Beatriz
Hafiz, Ehab O. A.
Muzikansky, Alona
van Gulik, Thomas M.
Markmann, James F.
Stott, Shannon L.
Yeh, Heidi
Toner, Mehmet
Uygun, Korkut
Tessier, Shannon N.
author_sort de Vries, Reinier J.
collection PubMed
description The global shortage of donor organs has made it crucial to deeply understand and better predict donor liver viability. However, biomarkers that effectively assess viability of marginal grafts for organ transplantation are currently lacking. Here, we showed that hepatocytes, sinusoidal endothelial, stellate, and liver-specific immune cells were released into perfusates from Lewis rat livers as a result of cold ischemia and machine perfusion. Perfusate comparison analysis of fresh livers and cold ischemic livers showed that the released cell profiles were significantly altered by the duration of cold ischemia. Our findings show for the first time that parenchymal cells are released from organs under non-proliferative pathological conditions, correlating with the degree of ischemic injury. Thus, perfusate cell profiles could serve as potential biomarkers of graft viability and indicators of specific injury mechanisms during organ handling and transplantation. Further, parenchymal cell release may have applications in other pathological conditions beyond organ transplantation.
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spelling pubmed-69812182020-01-30 Cell release during perfusion reflects cold ischemic injury in rat livers de Vries, Reinier J. Pendexter, Casie A. Cronin, Stephanie E. J. Marques, Beatriz Hafiz, Ehab O. A. Muzikansky, Alona van Gulik, Thomas M. Markmann, James F. Stott, Shannon L. Yeh, Heidi Toner, Mehmet Uygun, Korkut Tessier, Shannon N. Sci Rep Article The global shortage of donor organs has made it crucial to deeply understand and better predict donor liver viability. However, biomarkers that effectively assess viability of marginal grafts for organ transplantation are currently lacking. Here, we showed that hepatocytes, sinusoidal endothelial, stellate, and liver-specific immune cells were released into perfusates from Lewis rat livers as a result of cold ischemia and machine perfusion. Perfusate comparison analysis of fresh livers and cold ischemic livers showed that the released cell profiles were significantly altered by the duration of cold ischemia. Our findings show for the first time that parenchymal cells are released from organs under non-proliferative pathological conditions, correlating with the degree of ischemic injury. Thus, perfusate cell profiles could serve as potential biomarkers of graft viability and indicators of specific injury mechanisms during organ handling and transplantation. Further, parenchymal cell release may have applications in other pathological conditions beyond organ transplantation. Nature Publishing Group UK 2020-01-24 /pmc/articles/PMC6981218/ /pubmed/31980677 http://dx.doi.org/10.1038/s41598-020-57589-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
de Vries, Reinier J.
Pendexter, Casie A.
Cronin, Stephanie E. J.
Marques, Beatriz
Hafiz, Ehab O. A.
Muzikansky, Alona
van Gulik, Thomas M.
Markmann, James F.
Stott, Shannon L.
Yeh, Heidi
Toner, Mehmet
Uygun, Korkut
Tessier, Shannon N.
Cell release during perfusion reflects cold ischemic injury in rat livers
title Cell release during perfusion reflects cold ischemic injury in rat livers
title_full Cell release during perfusion reflects cold ischemic injury in rat livers
title_fullStr Cell release during perfusion reflects cold ischemic injury in rat livers
title_full_unstemmed Cell release during perfusion reflects cold ischemic injury in rat livers
title_short Cell release during perfusion reflects cold ischemic injury in rat livers
title_sort cell release during perfusion reflects cold ischemic injury in rat livers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981218/
https://www.ncbi.nlm.nih.gov/pubmed/31980677
http://dx.doi.org/10.1038/s41598-020-57589-4
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