Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice

Stem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4 liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4 injury. In vitro we gave CCl4 i...

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Main Authors: Sulaiman Shams, Sadia Mohsin, Ghazanfar Ali Nasir, Mohsin Khan, Shaheen N. Khan
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/747245
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author Sulaiman Shams
Sadia Mohsin
Ghazanfar Ali Nasir
Mohsin Khan
Shaheen N. Khan
author_facet Sulaiman Shams
Sadia Mohsin
Ghazanfar Ali Nasir
Mohsin Khan
Shaheen N. Khan
author_sort Sulaiman Shams
collection DOAJ
description Stem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4 liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4 injury. In vitro we gave CCl4 injury to mouse hepatocytes and cocultured it with untreated and cytokines pretreated MSCs. For in vivo study we labeled MSCs with PKH-26 and transplanted them into CCl4 injured mice by direct injection into liver. In vitro data showed that cytokines pretreated MSCs significantly reduce LDH level and apoptotic markers in CCl4 injured hepatocytes cocultured model. Furthermore the cytokines pretreated MSCs also improved cell viability and enhanced hepatic and antiapoptotic markers in injured hepatocytes cocultured model as compared to untreated MSCs. In vivo data in cytokines pretreated group demonstrated greater homing of MSCs in liver, restored glycogen storage, and significant reduction in collagen, alkaline phosphatase, and bilirubin levels. TUNEL assay and real time PCR also supported our hypothesis. Therefore, cytokines pretreated MSCs were shown to have a better therapeutic potential on reduction of liver injury. These results demonstrated the potential utility of this novel idea of cytokines pretreated MSCs for the treatment of liver fibrosis.
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institution Kabale University
issn 1687-966X
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publisher Wiley
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series Stem Cells International
spelling doaj-art-b0bd990e523b40e69925e460e16231f42025-02-03T01:31:33ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/747245747245Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in MiceSulaiman Shams0Sadia Mohsin1Ghazanfar Ali Nasir2Mohsin Khan3Shaheen N. Khan4National Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, PakistanNational Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, PakistanNational Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, PakistanNational Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, PakistanNational Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, PakistanStem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4 liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4 injury. In vitro we gave CCl4 injury to mouse hepatocytes and cocultured it with untreated and cytokines pretreated MSCs. For in vivo study we labeled MSCs with PKH-26 and transplanted them into CCl4 injured mice by direct injection into liver. In vitro data showed that cytokines pretreated MSCs significantly reduce LDH level and apoptotic markers in CCl4 injured hepatocytes cocultured model. Furthermore the cytokines pretreated MSCs also improved cell viability and enhanced hepatic and antiapoptotic markers in injured hepatocytes cocultured model as compared to untreated MSCs. In vivo data in cytokines pretreated group demonstrated greater homing of MSCs in liver, restored glycogen storage, and significant reduction in collagen, alkaline phosphatase, and bilirubin levels. TUNEL assay and real time PCR also supported our hypothesis. Therefore, cytokines pretreated MSCs were shown to have a better therapeutic potential on reduction of liver injury. These results demonstrated the potential utility of this novel idea of cytokines pretreated MSCs for the treatment of liver fibrosis.http://dx.doi.org/10.1155/2015/747245
spellingShingle Sulaiman Shams
Sadia Mohsin
Ghazanfar Ali Nasir
Mohsin Khan
Shaheen N. Khan
Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice
Stem Cells International
title Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice
title_full Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice
title_fullStr Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice
title_full_unstemmed Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice
title_short Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice
title_sort mesenchymal stem cells pretreated with hgf and fgf4 can reduce liver fibrosis in mice
url http://dx.doi.org/10.1155/2015/747245
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AT ghazanfaralinasir mesenchymalstemcellspretreatedwithhgfandfgf4canreduceliverfibrosisinmice
AT mohsinkhan mesenchymalstemcellspretreatedwithhgfandfgf4canreduceliverfibrosisinmice
AT shaheennkhan mesenchymalstemcellspretreatedwithhgfandfgf4canreduceliverfibrosisinmice