Liver Macrophage Depletion Ameliorates The Effect of Mesenchymal Stem Cell Transplantation in a Murine Model of Injured Liver

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Ghanem L.; Mansour I.M.; Abulata N.; Akl M.M.; Demerdash Z.A.; El Baz H.G.; Mahmoud S.S.; Mohamed S.H.; Mahmoud F.S.; Hassan A.S.M.

Journal: Scientific Reports

Publisher: Nature Publishing Group

Publication Date: 10 January 2019

Volume / Issue: Volume 9 / Issue 1

Article No.: 35

ISSN: 20452322

DOI: 10.1038/s41598-018-37184-4

Scopus: View on Scopus

PubMed: 30631109

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Ghanem L., Departments of Electron Microscopy, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Mansour I.M., Department of Clinical & Chemical pathology, Kasr Al-Ainy hospital, Faculty of medicine, Cairo University, Cairo, 11562, Egypt; Abulata N., Department of Clinical & Chemical pathology, Kasr Al-Ainy hospital, Faculty of medicine, Cairo University, Cairo, 11562, Egypt; Akl M.M., Department of Pathology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Demerdash Z.A., Department of Immunology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; El Baz H.G., Department of Immunology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Mahmoud S.S., Department of parasitology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Mohamed S.H., Department of Immunology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Mahmoud F.S., Department of Immunology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Hassan A.S.M., Departments of Electron Microscopy, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt

Abstract

Mesenchymal stem cells (MSCs) therapy show different levels of effectiveness in the context of different types of liver damage, suggesting that the microenvironment of the injured liver is a key determinant for effective stem cell therapy. The objective was to assess the modulatory effect of hepatic stem cell niche components on the transplanted MSCs during liver injury induced by carbon tetrachloride (CCl4). Superparamagnetic iron oxide (SPIO)-labeled human MSCs were injected intravenously into mice treated with CCl4 and subjected to hepatic macrophage-depletion. Liver tissues were collected at different intervals post transplantation for subsequent histopathological, morphometric, immunohistochemical, gene expression and ultrastructural studies. The homing of the transplanted MSCs was evidenced by tracing them within the niche by iron staining and immunohistochemical studies. MSCs differentiated into hepatocyte-like cells and intimal smooth muscle cells as evidenced by their expression of human albumin and α-smooth muscle actin with a concomitant increase in the level of mouse hepatocyte growth factor. A post transplantation reduction in the liver fibro-inflammatory reaction was found and was promoted by liver macrophages depletion. Thus, it could be concluded from the present study that prior manipulation of the microenvironment is required to improve the outcome of the transplanted cells. © 2019, The Author(s).

Keywords

Animals; Biometry; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Gene Expression Profiling; Histocytochemistry; Immunohistochemistry; Macrophages; Mesenchymal Stem Cell Transplantation; Mice; Treatment Outcome; animal; cytochemistry; disease model; immunology; macrophage; mouse; pathology; toxic hepatitis

Citation Information

Scopus Citations: 12

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