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...
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Wiley
2015-01-01
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Series: | Journal of Immunology Research |
Online Access: | http://dx.doi.org/10.1155/2015/202975 |
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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 |
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