Naglaa K Idriss1, Hayam G Sayyed2, Amany Osama1, Dina Sabry3. 1. Departments of Medical Biochemistry, Assiut, Egypt. 2. Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt. 3. Department of Medical Biochemistry and Molecular Biology Faculty of Medicine, Cairo University, Cairo, Egypt.
Abstract
BACKGROUND/AIMS: The most appropriate route for bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in the management of liver fibrosis remains controversial. This study investigated the therapeutic efficacy of intravenous and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced rat liver fibrosis. METHODS: Fifty rats were divided into 5 groups (n = 10 rats per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated, labeled with green fluorescent protein (GFP), and injected into fibrotic rats either intravenously or intrasplenically. Gene expression of interleukins (IL-1β and IL-6), interferon (INF)-γ, hepatic growth factor, and the hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time reverse transcription-polymerase chain reaction. Vascular endothelial growth factor and connective tissue growth factor was detected by western blot analysis and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver tissue. RESULTS: Both routes achieved a similar enhancement of liver function, which was confirmed by histopathological examination. The intravenous route was more effective than the intrasplenic route in reducing gene expression levels of IL-1β, IL-6, and INF-γ. However, fibrotic changes were still observed in the recovery group. CONCLUSION: Intravenous BM-MSC injection was an efficient and appropriate route for BM-MSC transplantation for the management of liver fibrosis.
BACKGROUND/AIMS: The most appropriate route for bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in the management of liver fibrosis remains controversial. This study investigated the therapeutic efficacy of intravenous and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced ratliver fibrosis. METHODS: Fifty rats were divided into 5 groups (n = 10 rats per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated, labeled with green fluorescent protein (GFP), and injected into fibrotic rats either intravenously or intrasplenically. Gene expression of interleukins (IL-1β and IL-6), interferon (INF)-γ, hepatic growth factor, and the hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time reverse transcription-polymerase chain reaction. Vascular endothelial growth factor and connective tissue growth factor was detected by western blot analysis and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver tissue. RESULTS: Both routes achieved a similar enhancement of liver function, which was confirmed by histopathological examination. The intravenous route was more effective than the intrasplenic route in reducing gene expression levels of IL-1β, IL-6, and INF-γ. However, fibrotic changes were still observed in the recovery group. CONCLUSION: Intravenous BM-MSC injection was an efficient and appropriate route for BM-MSC transplantation for the management of liver fibrosis.