Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies

Despite reports of the successful isolation of primary equine hepatocytes, thereare no published data regarding the successful cryopreservation of these isolatedcells. In this study, a detailed description of the procedures for isolation, cryop-reservation, and recovery of equine hepatocytes are pre...

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Main Authors: Shibany, Khaled A., Tötemeyer, Sabine, Pratt, Stefanie L., Paine, Stuart W.
Format: Article
Published: Wiley 2016
Subjects:
Online Access:https://eprints.nottingham.ac.uk/37532/
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author Shibany, Khaled A.
Tötemeyer, Sabine
Pratt, Stefanie L.
Paine, Stuart W.
author_facet Shibany, Khaled A.
Tötemeyer, Sabine
Pratt, Stefanie L.
Paine, Stuart W.
author_sort Shibany, Khaled A.
building Nottingham Research Data Repository
collection Online Access
description Despite reports of the successful isolation of primary equine hepatocytes, thereare no published data regarding the successful cryopreservation of these isolatedcells. In this study, a detailed description of the procedures for isolation, cryop-reservation, and recovery of equine hepatocytes are presented. Furthermore, theintrinsic clearance (Clint) and production of metabolites for three drugs werecompared between freshly isolated and recovered cryopreserved hepatocytes. Pri-mary equine hepatocytes were isolated using a two-step collagenase perfusionmethod, with an average cell yield of 2.47  2.62 9 106cells/g of perfused livertissue and viability of 84.1  2.62%. These cells were cryopreserved with Wil-liam’s medium E containing 10% fetal bovine serum with 10% DMSO. The via-bility of recovered cells, after a 30% Percoll gradient, was 77  11% andestimated recovery rate was approximately 27%. These purified cells were usedto determine the in vitro Clintof three drugs used in equine medicine; omepra-zole, flunixin, and phenylbutazone, via the substrate depletion method. Cryopre-served suspensions gave a comparable estimation of Clintcompared to fresh cellsfor these three drugs as well as producing the same metabolites. This work pavesthe way for establishing a bank of cryopreserved equine hepatocytes that can beused for estimating pharmacokinetic parameters such as the hepatic metabolicin vivo clearance of a drug as well as producing horse-specific drug metabolites.
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spelling nottingham-375322020-05-04T18:09:02Z https://eprints.nottingham.ac.uk/37532/ Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies Shibany, Khaled A. Tötemeyer, Sabine Pratt, Stefanie L. Paine, Stuart W. Despite reports of the successful isolation of primary equine hepatocytes, thereare no published data regarding the successful cryopreservation of these isolatedcells. In this study, a detailed description of the procedures for isolation, cryop-reservation, and recovery of equine hepatocytes are presented. Furthermore, theintrinsic clearance (Clint) and production of metabolites for three drugs werecompared between freshly isolated and recovered cryopreserved hepatocytes. Pri-mary equine hepatocytes were isolated using a two-step collagenase perfusionmethod, with an average cell yield of 2.47  2.62 9 106cells/g of perfused livertissue and viability of 84.1  2.62%. These cells were cryopreserved with Wil-liam’s medium E containing 10% fetal bovine serum with 10% DMSO. The via-bility of recovered cells, after a 30% Percoll gradient, was 77  11% andestimated recovery rate was approximately 27%. These purified cells were usedto determine the in vitro Clintof three drugs used in equine medicine; omepra-zole, flunixin, and phenylbutazone, via the substrate depletion method. Cryopre-served suspensions gave a comparable estimation of Clintcompared to fresh cellsfor these three drugs as well as producing the same metabolites. This work pavesthe way for establishing a bank of cryopreserved equine hepatocytes that can beused for estimating pharmacokinetic parameters such as the hepatic metabolicin vivo clearance of a drug as well as producing horse-specific drug metabolites. Wiley 2016-09-30 Article PeerReviewed Shibany, Khaled A., Tötemeyer, Sabine, Pratt, Stefanie L. and Paine, Stuart W. (2016) Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies. Pharmacology Research and Perspectives, 4 (5). e00268. ISSN 2052-1707 Cell viability; cryopreservation; drug metabolism; equine; hepatocyte isolation http://onlinelibrary.wiley.com/doi/10.1002/prp2.268/abstract doi:10.1002/prp2.268 doi:10.1002/prp2.268
spellingShingle Cell viability; cryopreservation; drug metabolism; equine; hepatocyte isolation
Shibany, Khaled A.
Tötemeyer, Sabine
Pratt, Stefanie L.
Paine, Stuart W.
Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
title Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
title_full Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
title_fullStr Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
title_full_unstemmed Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
title_short Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
title_sort equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
topic Cell viability; cryopreservation; drug metabolism; equine; hepatocyte isolation
url https://eprints.nottingham.ac.uk/37532/
https://eprints.nottingham.ac.uk/37532/
https://eprints.nottingham.ac.uk/37532/