Cold-preservation of human adult hepatocytes for liver cell therapy

Duret, C. (Cedric)|||/items/2bba41c0-0905-4327-8fea-589b13b5fae7; Moreno, D. (D.)|||/items/127524c3-b325-4c6a-b92f-7d57cb4a3eb7; Balasiddaiah, A. (Anangi)|||/items/ec40a28a-ac77-4401-bc86-40a2ee9322b3; Roux, S. (Solene)|||/items/9a3b9630-cb29-482d-9475-a51169d16956; Briolotti, P. (Phillipe)|||/items/89169c54-b25d-44ed-b67d-9ba551061262; Raulet, E. (Edith)|||/items/356e9d58-7688-44f4-b4d7-a927b543ba4b; Herrero, A. (Astrid)|||/items/e84ffca7-c865-474f-8792-ba9eb7b6dd31; Ramet, H. (Helene)|||/items/d448ed3f-36b9-4d21-92bb-a159019cf1f7; Biron-Andreani, C. (Christine)|||/items/a5405f82-52d9-4ee0-b1b8-d5b2efb67252; Gerbal-Chaloin, S. (Sabine)|||/items/f2c3cbdb-ddf3-43a0-9948-0b118704aaa3; Ramos, J. (Jeanne)|||/items/7407946f-6051-422e-82b5-333a95e8b065; Navarro, F. (Francis)|||/items/72008b9c-5ce4-4c21-b925-23d9b4c91792; Hardwigsen, J. (Jean)|||/items/da4aa1c3-6980-4061-bff7-4949f7f3b3b6; Maurel, P. (Patrick)|||/items/446ac0cd-8584-48fd-a718-557516d0afa3; Aldabe, R. (Rafael)|||/items/ef60614f-7fda-4565-bd52-0ace35b55292; Daujat-Chavanieu, M. (M.)|||/items/fb4a5f83-cabb-46f7-bbf1-49aa40dcbdaf

Cold-preservation of human adult hepatocytes for liver cell therapy

Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in s...

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Authors:	Duret, C. (Cedric)\|\|\|/items/2bba41c0-0905-4327-8fea-589b13b5fae7, Moreno, D. (D.)\|\|\|/items/127524c3-b325-4c6a-b92f-7d57cb4a3eb7, Balasiddaiah, A. (Anangi)\|\|\|/items/ec40a28a-ac77-4401-bc86-40a2ee9322b3, Roux, S. (Solene)\|\|\|/items/9a3b9630-cb29-482d-9475-a51169d16956, Briolotti, P. (Phillipe)\|\|\|/items/89169c54-b25d-44ed-b67d-9ba551061262, Raulet, E. (Edith)\|\|\|/items/356e9d58-7688-44f4-b4d7-a927b543ba4b, Herrero, A. (Astrid)\|\|\|/items/e84ffca7-c865-474f-8792-ba9eb7b6dd31, Ramet, H. (Helene)\|\|\|/items/d448ed3f-36b9-4d21-92bb-a159019cf1f7, Biron-Andreani, C. (Christine)\|\|\|/items/a5405f82-52d9-4ee0-b1b8-d5b2efb67252, Gerbal-Chaloin, S. (Sabine)\|\|\|/items/f2c3cbdb-ddf3-43a0-9948-0b118704aaa3, Ramos, J. (Jeanne)\|\|\|/items/7407946f-6051-422e-82b5-333a95e8b065, Navarro, F. (Francis)\|\|\|/items/72008b9c-5ce4-4c21-b925-23d9b4c91792, Hardwigsen, J. (Jean)\|\|\|/items/da4aa1c3-6980-4061-bff7-4949f7f3b3b6, Maurel, P. (Patrick)\|\|\|/items/446ac0cd-8584-48fd-a718-557516d0afa3, Aldabe, R. (Rafael)\|\|\|/items/ef60614f-7fda-4565-bd52-0ace35b55292, Daujat-Chavanieu, M. (M.)\|\|\|/items/fb4a5f83-cabb-46f7-bbf1-49aa40dcbdaf
Format:	article
Publication Date:	2015
Country:	España
Institution:	Universidad de Navarra
Repository:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:	English
OAI Identifier:	oai:dadun.unav.edu:10171/38249
Online Access:	https://hdl.handle.net/10171/38249
Access Level:	Open access
Keyword:	Liver Human hepatocytes Cell therapy Engraftment Hypothermic preservation Transplantation

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spelling	Cold-preservation of human adult hepatocytes for liver cell therapyDuret, C. (Cedric)\|\|\|/items/2bba41c0-0905-4327-8fea-589b13b5fae7Moreno, D. (D.)\|\|\|/items/127524c3-b325-4c6a-b92f-7d57cb4a3eb7Balasiddaiah, A. (Anangi)\|\|\|/items/ec40a28a-ac77-4401-bc86-40a2ee9322b3Roux, S. (Solene)\|\|\|/items/9a3b9630-cb29-482d-9475-a51169d16956Briolotti, P. (Phillipe)\|\|\|/items/89169c54-b25d-44ed-b67d-9ba551061262Raulet, E. (Edith)\|\|\|/items/356e9d58-7688-44f4-b4d7-a927b543ba4bHerrero, A. (Astrid)\|\|\|/items/e84ffca7-c865-474f-8792-ba9eb7b6dd31Ramet, H. (Helene)\|\|\|/items/d448ed3f-36b9-4d21-92bb-a159019cf1f7Biron-Andreani, C. (Christine)\|\|\|/items/a5405f82-52d9-4ee0-b1b8-d5b2efb67252Gerbal-Chaloin, S. (Sabine)\|\|\|/items/f2c3cbdb-ddf3-43a0-9948-0b118704aaa3Ramos, J. (Jeanne)\|\|\|/items/7407946f-6051-422e-82b5-333a95e8b065Navarro, F. (Francis)\|\|\|/items/72008b9c-5ce4-4c21-b925-23d9b4c91792Hardwigsen, J. (Jean)\|\|\|/items/da4aa1c3-6980-4061-bff7-4949f7f3b3b6Maurel, P. (Patrick)\|\|\|/items/446ac0cd-8584-48fd-a718-557516d0afa3Aldabe, R. (Rafael)\|\|\|/items/ef60614f-7fda-4565-bd52-0ace35b55292Daujat-Chavanieu, M. (M.)\|\|\|/items/fb4a5f83-cabb-46f7-bbf1-49aa40dcbdafLiverHuman hepatocytesCell therapyEngraftmentHypothermic preservationTransplantationHepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation.Cognizant Communication CorporationDadun. Depósito Académico Digital Universidad de Navarra20152015-05-0720152015-01-0120152015-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/38249reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/382492026-06-21T12:47:57Z
dc.title.none.fl_str_mv	Cold-preservation of human adult hepatocytes for liver cell therapy
title	Cold-preservation of human adult hepatocytes for liver cell therapy
spellingShingle	Cold-preservation of human adult hepatocytes for liver cell therapy Duret, C. (Cedric)\|\|\|/items/2bba41c0-0905-4327-8fea-589b13b5fae7 Liver Human hepatocytes Cell therapy Engraftment Hypothermic preservation Transplantation
title_short	Cold-preservation of human adult hepatocytes for liver cell therapy
title_full	Cold-preservation of human adult hepatocytes for liver cell therapy
title_fullStr	Cold-preservation of human adult hepatocytes for liver cell therapy
title_full_unstemmed	Cold-preservation of human adult hepatocytes for liver cell therapy
title_sort	Cold-preservation of human adult hepatocytes for liver cell therapy
dc.creator.none.fl_str_mv	Duret, C. (Cedric)\|\|\|/items/2bba41c0-0905-4327-8fea-589b13b5fae7 Moreno, D. (D.)\|\|\|/items/127524c3-b325-4c6a-b92f-7d57cb4a3eb7 Balasiddaiah, A. (Anangi)\|\|\|/items/ec40a28a-ac77-4401-bc86-40a2ee9322b3 Roux, S. (Solene)\|\|\|/items/9a3b9630-cb29-482d-9475-a51169d16956 Briolotti, P. (Phillipe)\|\|\|/items/89169c54-b25d-44ed-b67d-9ba551061262 Raulet, E. (Edith)\|\|\|/items/356e9d58-7688-44f4-b4d7-a927b543ba4b Herrero, A. (Astrid)\|\|\|/items/e84ffca7-c865-474f-8792-ba9eb7b6dd31 Ramet, H. (Helene)\|\|\|/items/d448ed3f-36b9-4d21-92bb-a159019cf1f7 Biron-Andreani, C. (Christine)\|\|\|/items/a5405f82-52d9-4ee0-b1b8-d5b2efb67252 Gerbal-Chaloin, S. (Sabine)\|\|\|/items/f2c3cbdb-ddf3-43a0-9948-0b118704aaa3 Ramos, J. (Jeanne)\|\|\|/items/7407946f-6051-422e-82b5-333a95e8b065 Navarro, F. (Francis)\|\|\|/items/72008b9c-5ce4-4c21-b925-23d9b4c91792 Hardwigsen, J. (Jean)\|\|\|/items/da4aa1c3-6980-4061-bff7-4949f7f3b3b6 Maurel, P. (Patrick)\|\|\|/items/446ac0cd-8584-48fd-a718-557516d0afa3 Aldabe, R. (Rafael)\|\|\|/items/ef60614f-7fda-4565-bd52-0ace35b55292 Daujat-Chavanieu, M. (M.)\|\|\|/items/fb4a5f83-cabb-46f7-bbf1-49aa40dcbdaf
author	Duret, C. (Cedric)\|\|\|/items/2bba41c0-0905-4327-8fea-589b13b5fae7
author_facet	Duret, C. (Cedric)\|\|\|/items/2bba41c0-0905-4327-8fea-589b13b5fae7 Moreno, D. (D.)\|\|\|/items/127524c3-b325-4c6a-b92f-7d57cb4a3eb7 Balasiddaiah, A. (Anangi)\|\|\|/items/ec40a28a-ac77-4401-bc86-40a2ee9322b3 Roux, S. (Solene)\|\|\|/items/9a3b9630-cb29-482d-9475-a51169d16956 Briolotti, P. (Phillipe)\|\|\|/items/89169c54-b25d-44ed-b67d-9ba551061262 Raulet, E. (Edith)\|\|\|/items/356e9d58-7688-44f4-b4d7-a927b543ba4b Herrero, A. (Astrid)\|\|\|/items/e84ffca7-c865-474f-8792-ba9eb7b6dd31 Ramet, H. (Helene)\|\|\|/items/d448ed3f-36b9-4d21-92bb-a159019cf1f7 Biron-Andreani, C. (Christine)\|\|\|/items/a5405f82-52d9-4ee0-b1b8-d5b2efb67252 Gerbal-Chaloin, S. (Sabine)\|\|\|/items/f2c3cbdb-ddf3-43a0-9948-0b118704aaa3 Ramos, J. (Jeanne)\|\|\|/items/7407946f-6051-422e-82b5-333a95e8b065 Navarro, F. (Francis)\|\|\|/items/72008b9c-5ce4-4c21-b925-23d9b4c91792 Hardwigsen, J. (Jean)\|\|\|/items/da4aa1c3-6980-4061-bff7-4949f7f3b3b6 Maurel, P. (Patrick)\|\|\|/items/446ac0cd-8584-48fd-a718-557516d0afa3 Aldabe, R. (Rafael)\|\|\|/items/ef60614f-7fda-4565-bd52-0ace35b55292 Daujat-Chavanieu, M. (M.)\|\|\|/items/fb4a5f83-cabb-46f7-bbf1-49aa40dcbdaf
author_role	author
author2	Moreno, D. (D.)\|\|\|/items/127524c3-b325-4c6a-b92f-7d57cb4a3eb7 Balasiddaiah, A. (Anangi)\|\|\|/items/ec40a28a-ac77-4401-bc86-40a2ee9322b3 Roux, S. (Solene)\|\|\|/items/9a3b9630-cb29-482d-9475-a51169d16956 Briolotti, P. (Phillipe)\|\|\|/items/89169c54-b25d-44ed-b67d-9ba551061262 Raulet, E. (Edith)\|\|\|/items/356e9d58-7688-44f4-b4d7-a927b543ba4b Herrero, A. (Astrid)\|\|\|/items/e84ffca7-c865-474f-8792-ba9eb7b6dd31 Ramet, H. (Helene)\|\|\|/items/d448ed3f-36b9-4d21-92bb-a159019cf1f7 Biron-Andreani, C. (Christine)\|\|\|/items/a5405f82-52d9-4ee0-b1b8-d5b2efb67252 Gerbal-Chaloin, S. (Sabine)\|\|\|/items/f2c3cbdb-ddf3-43a0-9948-0b118704aaa3 Ramos, J. (Jeanne)\|\|\|/items/7407946f-6051-422e-82b5-333a95e8b065 Navarro, F. (Francis)\|\|\|/items/72008b9c-5ce4-4c21-b925-23d9b4c91792 Hardwigsen, J. (Jean)\|\|\|/items/da4aa1c3-6980-4061-bff7-4949f7f3b3b6 Maurel, P. (Patrick)\|\|\|/items/446ac0cd-8584-48fd-a718-557516d0afa3 Aldabe, R. (Rafael)\|\|\|/items/ef60614f-7fda-4565-bd52-0ace35b55292 Daujat-Chavanieu, M. (M.)\|\|\|/items/fb4a5f83-cabb-46f7-bbf1-49aa40dcbdaf
author2_role	author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv	Liver Human hepatocytes Cell therapy Engraftment Hypothermic preservation Transplantation
topic	Liver Human hepatocytes Cell therapy Engraftment Hypothermic preservation Transplantation
description	Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation.
publishDate	2015
dc.date.none.fl_str_mv	2015 2015-05-07 2015 2015-01-01 2015 2015-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/38249
url	https://hdl.handle.net/10171/38249
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Cognizant Communication Corporation
publisher.none.fl_str_mv	Cognizant Communication Corporation
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra
instname_str	Universidad de Navarra
reponame_str	Dadun. Depósito Académico Digital de la Universidad de Navarra
collection	Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,301603

Cold-preservation of human adult hepatocytes for liver cell therapy

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