Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion

Porcine hepatocytes transplanted during acute liver failure might support metabolic functions until the diseased liver recovers its function. Here, we isolated high numbers of viable pig hepatocytes and evaluated hepatocyte functionality after encapsulation. We further investigated whether coculture...

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Main Authors: Elisa Montanari, Joel Pimenta, Luca Szabó, François Noverraz, Solène Passemard, Raphael P. H. Meier, Jeremy Meyer, Jonathan Sidibe, Aurelien Thomas, Henk-Jan Schuurman, Sandrine Gerber-Lemaire, Carmen Gonelle-Gispert, Leo H. Buhler
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/1078547
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author Elisa Montanari
Joel Pimenta
Luca Szabó
François Noverraz
Solène Passemard
Raphael P. H. Meier
Jeremy Meyer
Jonathan Sidibe
Aurelien Thomas
Henk-Jan Schuurman
Sandrine Gerber-Lemaire
Carmen Gonelle-Gispert
Leo H. Buhler
author_facet Elisa Montanari
Joel Pimenta
Luca Szabó
François Noverraz
Solène Passemard
Raphael P. H. Meier
Jeremy Meyer
Jonathan Sidibe
Aurelien Thomas
Henk-Jan Schuurman
Sandrine Gerber-Lemaire
Carmen Gonelle-Gispert
Leo H. Buhler
author_sort Elisa Montanari
collection DOAJ
description Porcine hepatocytes transplanted during acute liver failure might support metabolic functions until the diseased liver recovers its function. Here, we isolated high numbers of viable pig hepatocytes and evaluated hepatocyte functionality after encapsulation. We further investigated whether coculture and coencapsulation of hepatocytes with human multipotent mesenchymal stromal cells (MSC) are beneficial on hepatocyte function. Livers from 10 kg pigs (n=9) were harvested, and hepatocytes were isolated from liver suspensions for microencapsulation using alginate and poly(ethylene-glycol)- (PEG-) grafted alginate hydrogels, either alone or in combination with MSC. Viability, albumin secretion, and diazepam catabolism of hepatocytes were measured for one week. 9.2 ± 3.6 × 109 hepatocytes with 95.2 ± 3.1% viability were obtained after isolation. At day 3, free hepatocytes displayed 99% viability, whereas microencapsulation in alginate and PEG-grafted alginate decreased viability to 62% and 48%, respectively. Albumin secretion and diazepam catabolism occurred in free and microencapsulated hepatocytes. Coencapsulation of hepatocytes with MSC significantly improved viability and albumin secretion at days 4 and 8 (p<0.05). Coculture with MSC significantly increased and prolonged albumin secretion. In conclusion, we established a protocol for isolation and microencapsulation of high numbers of viable pig hepatocytes and demonstrated that the presence of MSC is beneficial for the viability and function of porcine hepatocytes.
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spelling doaj-art-da70ff0595a744299c989f54c23f18de2025-02-03T06:01:22ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/10785471078547Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin SecretionElisa Montanari0Joel Pimenta1Luca Szabó2François Noverraz3Solène Passemard4Raphael P. H. Meier5Jeremy Meyer6Jonathan Sidibe7Aurelien Thomas8Henk-Jan Schuurman9Sandrine Gerber-Lemaire10Carmen Gonelle-Gispert11Leo H. Buhler12Department of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandDepartment of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandInstitute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, SwitzerlandInstitute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, SwitzerlandInstitute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, SwitzerlandDepartment of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandDepartment of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandUniversity Centre of Legal Medicine, Universities of Lausanne and Geneva, Lausanne, SwitzerlandUniversity Centre of Legal Medicine, Universities of Lausanne and Geneva, Lausanne, SwitzerlandDepartment of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandInstitute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, SwitzerlandDepartment of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandDepartment of Surgery, Geneva University Hospitals and Medical Faculty, 1211 Geneva, SwitzerlandPorcine hepatocytes transplanted during acute liver failure might support metabolic functions until the diseased liver recovers its function. Here, we isolated high numbers of viable pig hepatocytes and evaluated hepatocyte functionality after encapsulation. We further investigated whether coculture and coencapsulation of hepatocytes with human multipotent mesenchymal stromal cells (MSC) are beneficial on hepatocyte function. Livers from 10 kg pigs (n=9) were harvested, and hepatocytes were isolated from liver suspensions for microencapsulation using alginate and poly(ethylene-glycol)- (PEG-) grafted alginate hydrogels, either alone or in combination with MSC. Viability, albumin secretion, and diazepam catabolism of hepatocytes were measured for one week. 9.2 ± 3.6 × 109 hepatocytes with 95.2 ± 3.1% viability were obtained after isolation. At day 3, free hepatocytes displayed 99% viability, whereas microencapsulation in alginate and PEG-grafted alginate decreased viability to 62% and 48%, respectively. Albumin secretion and diazepam catabolism occurred in free and microencapsulated hepatocytes. Coencapsulation of hepatocytes with MSC significantly improved viability and albumin secretion at days 4 and 8 (p<0.05). Coculture with MSC significantly increased and prolonged albumin secretion. In conclusion, we established a protocol for isolation and microencapsulation of high numbers of viable pig hepatocytes and demonstrated that the presence of MSC is beneficial for the viability and function of porcine hepatocytes.http://dx.doi.org/10.1155/2018/1078547
spellingShingle Elisa Montanari
Joel Pimenta
Luca Szabó
François Noverraz
Solène Passemard
Raphael P. H. Meier
Jeremy Meyer
Jonathan Sidibe
Aurelien Thomas
Henk-Jan Schuurman
Sandrine Gerber-Lemaire
Carmen Gonelle-Gispert
Leo H. Buhler
Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion
Journal of Immunology Research
title Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion
title_full Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion
title_fullStr Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion
title_full_unstemmed Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion
title_short Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion
title_sort beneficial effects of human mesenchymal stromal cells on porcine hepatocyte viability and albumin secretion
url http://dx.doi.org/10.1155/2018/1078547
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