The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats

Mesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therapies for acute liver failure (ALF). The cotransplantation of hepatocytes with MSCs can improve the therapeutic performance for the treatment of ALF. However, the therapeutic potential of conditioned medium (C...

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Main Authors: Li Chen, Jiexin Zhang, Lu Yang, Guoying Zhang, Yingjie Wang, Shichang Zhang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/9156560
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author Li Chen
Jiexin Zhang
Lu Yang
Guoying Zhang
Yingjie Wang
Shichang Zhang
author_facet Li Chen
Jiexin Zhang
Lu Yang
Guoying Zhang
Yingjie Wang
Shichang Zhang
author_sort Li Chen
collection DOAJ
description Mesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therapies for acute liver failure (ALF). The cotransplantation of hepatocytes with MSCs can improve the therapeutic performance for the treatment of ALF. However, the therapeutic potential of conditioned medium (CM) derived from MSCs cocultured with hepatocytes (MSC-H-CM) remains unclear. The purpose of this study was to investigate the effects of MSC-H-CM on damaged hepatocytes in vitro and on D-galactosamine-induced ALF in vivo. D-Galactosamine-treated L02 cells cultured in MSC-H-CM exhibited higher of cell viability and total protein synthesis than L02 cells cultured in MSC-CM, CM derived from hepatocytes (H-CM), MSC-CM + H-CM, or with nonconditioned medium (NCM). Lactate dehydrogenase and aspartate aminotransferase levels were lower in the supernatant of damaged L02 cells cultured in MSC-H-CM than in that of L02 cells cultured in other types of CM. The lowest percentage of apoptotic cells was observed after the MSC-H-CM treatment. When CM was injected into the tail vein of rats with ALF, MSC-H-CM was the most successful at preventing the release of liver injury biomarkers and in promoting the recovery of liver structure. The greatest survival rate 7 days after the first treatment was observed in the MSC-H-CM-treated rats. Our results reveal that the delivery of MSC-H-CM could be a novel strategy for integrating the therapeutic potentials of hepatocytes and MSCs for the treatment of ALF.
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spelling doaj-art-008cf032eee94c38bcc9bbe7b0b25a9b2025-08-20T03:22:31ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/91565609156560The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in RatsLi Chen0Jiexin Zhang1Lu Yang2Guoying Zhang3Yingjie Wang4Shichang Zhang5Department of Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaInstitute of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, ChinaMesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therapies for acute liver failure (ALF). The cotransplantation of hepatocytes with MSCs can improve the therapeutic performance for the treatment of ALF. However, the therapeutic potential of conditioned medium (CM) derived from MSCs cocultured with hepatocytes (MSC-H-CM) remains unclear. The purpose of this study was to investigate the effects of MSC-H-CM on damaged hepatocytes in vitro and on D-galactosamine-induced ALF in vivo. D-Galactosamine-treated L02 cells cultured in MSC-H-CM exhibited higher of cell viability and total protein synthesis than L02 cells cultured in MSC-CM, CM derived from hepatocytes (H-CM), MSC-CM + H-CM, or with nonconditioned medium (NCM). Lactate dehydrogenase and aspartate aminotransferase levels were lower in the supernatant of damaged L02 cells cultured in MSC-H-CM than in that of L02 cells cultured in other types of CM. The lowest percentage of apoptotic cells was observed after the MSC-H-CM treatment. When CM was injected into the tail vein of rats with ALF, MSC-H-CM was the most successful at preventing the release of liver injury biomarkers and in promoting the recovery of liver structure. The greatest survival rate 7 days after the first treatment was observed in the MSC-H-CM-treated rats. Our results reveal that the delivery of MSC-H-CM could be a novel strategy for integrating the therapeutic potentials of hepatocytes and MSCs for the treatment of ALF.http://dx.doi.org/10.1155/2018/9156560
spellingShingle Li Chen
Jiexin Zhang
Lu Yang
Guoying Zhang
Yingjie Wang
Shichang Zhang
The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats
Stem Cells International
title The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats
title_full The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats
title_fullStr The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats
title_full_unstemmed The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats
title_short The Effects of Conditioned Medium Derived from Mesenchymal Stem Cells Cocultured with Hepatocytes on Damaged Hepatocytes and Acute Liver Failure in Rats
title_sort effects of conditioned medium derived from mesenchymal stem cells cocultured with hepatocytes on damaged hepatocytes and acute liver failure in rats
url http://dx.doi.org/10.1155/2018/9156560
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