Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion

Reinier J. de Vries; Stephanie E.J. Cronin; Padraic Romfh; Casie A. Pendexter; Rohil Jain; Benjamin T. Wilks; Siavash Raigani; Thomas M. van Gulik; Peili Chen; Heidi Yeh; Korkut Uygun; Shannon N. Tessier

doi:10.1371/journal.pone.0258833

Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion

Reinier J. de Vries, Stephanie E.J. Cronin, Padraic Romfh, Casie A. Pendexter, Rohil Jain, Benjamin T. Wilks, Siavash Raigani, Thomas M. van Gulik, Peili Chen, Heidi Yeh, Korkut Uygun, Shannon N. Tessier

Advanced Technologies for Preservation of Biological Systems

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

Original language	English (US)
Article number	e0258833
Journal	PloS one
Volume	16
Issue number	10 October
DOIs	https://doi.org/10.1371/journal.pone.0258833
State	Published - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 de Vries et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

EEC 1941543

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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title = "Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion",

abstract = "Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI. ",

author = "{de Vries}, {Reinier J.} and Cronin, {Stephanie E.J.} and Padraic Romfh and Pendexter, {Casie A.} and Rohil Jain and Wilks, {Benjamin T.} and Siavash Raigani and {van Gulik}, {Thomas M.} and Peili Chen and Heidi Yeh and Korkut Uygun and Tessier, {Shannon N.}",

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year = "2021",

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AU - de Vries, Reinier J.

AU - Cronin, Stephanie E.J.

AU - Romfh, Padraic

AU - Pendexter, Casie A.

AU - Jain, Rohil

AU - Wilks, Benjamin T.

AU - Raigani, Siavash

AU - van Gulik, Thomas M.

AU - Chen, Peili

AU - Yeh, Heidi

AU - Uygun, Korkut

AU - Tessier, Shannon N.

N1 - Publisher Copyright: © 2021 de Vries et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. EEC 1941543

PY - 2021/10

Y1 - 2021/10

N2 - Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

AB - Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

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Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion

Abstract

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ATP-Bio: NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio)

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Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion

Abstract

Bibliographical note

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ATP-Bio: NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio)

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