Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury

Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived...

Full description

Saved in:
Bibliographic Details
Main Authors: Suomi M. G. Fouraschen, Joshua H. Wolf, Luc J. W. van der Laan, Petra E. de Ruiter, Wayne W. Hancock, Job P. van Kooten, Monique M. A. Verstegen, Kim M. Olthoff, Jeroen de Jonge
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/202975
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832550616231051264
author Suomi M. G. Fouraschen
Joshua H. Wolf
Luc J. W. van der Laan
Petra E. de Ruiter
Wayne W. Hancock
Job P. van Kooten
Monique M. A. Verstegen
Kim M. Olthoff
Jeroen de Jonge
author_facet Suomi M. G. Fouraschen
Joshua H. Wolf
Luc J. W. van der Laan
Petra E. de Ruiter
Wayne W. Hancock
Job P. van Kooten
Monique M. A. Verstegen
Kim M. Olthoff
Jeroen de Jonge
author_sort Suomi M. G. Fouraschen
collection DOAJ
description Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrificed after 6 or 24 hours (IRI group) or after 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and inflammatory cytokine gene expression showed no significant differences between both treatment groups. In the IRI + PH model, significant reduction in hepatic tissue damage as well as a significant increase in hepatocyte proliferation was observed after MSC-CM treatment. Conclusion. Mesenchymal stromal cell-derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure.
format Article
id doaj-art-43f5c26d0b764f9383ad79ead67b11f5
institution Kabale University
issn 2314-8861
2314-7156
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-43f5c26d0b764f9383ad79ead67b11f52025-02-03T06:06:13ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/202975202975Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion InjurySuomi M. G. Fouraschen0Joshua H. Wolf1Luc J. W. van der Laan2Petra E. de Ruiter3Wayne W. Hancock4Job P. van Kooten5Monique M. A. Verstegen6Kim M. Olthoff7Jeroen de Jonge8Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, NetherlandsDepartment of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, NetherlandsDepartment of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, NetherlandsDepartment of Transplant Immunology, Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104-4318, USADepartment of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, NetherlandsDepartment of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, NetherlandsDepartment of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, NetherlandsLoss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrificed after 6 or 24 hours (IRI group) or after 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and inflammatory cytokine gene expression showed no significant differences between both treatment groups. In the IRI + PH model, significant reduction in hepatic tissue damage as well as a significant increase in hepatocyte proliferation was observed after MSC-CM treatment. Conclusion. Mesenchymal stromal cell-derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure.http://dx.doi.org/10.1155/2015/202975
spellingShingle Suomi M. G. Fouraschen
Joshua H. Wolf
Luc J. W. van der Laan
Petra E. de Ruiter
Wayne W. Hancock
Job P. van Kooten
Monique M. A. Verstegen
Kim M. Olthoff
Jeroen de Jonge
Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury
Journal of Immunology Research
title Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury
title_full Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury
title_fullStr Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury
title_full_unstemmed Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury
title_short Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury
title_sort mesenchymal stromal cell derived factors promote tissue repair in a small for size ischemic liver model but do not protect against early effects of ischemia and reperfusion injury
url http://dx.doi.org/10.1155/2015/202975
work_keys_str_mv AT suomimgfouraschen mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT joshuahwolf mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT lucjwvanderlaan mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT petraederuiter mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT waynewhancock mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT jobpvankooten mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT moniquemaverstegen mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT kimmolthoff mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury
AT jeroendejonge mesenchymalstromalcellderivedfactorspromotetissuerepairinasmallforsizeischemiclivermodelbutdonotprotectagainstearlyeffectsofischemiaandreperfusioninjury