Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model

Cell Physiol Biochem. 2018;48(5):2161-2171. doi: 10.1159/000492558. Epub 2018 Aug 16.

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.

Keywords: BM-MSCs; Liver fibrosis; Rats; Transplantation route.

MeSH terms

  • Actins / metabolism
  • Administration, Intravenous
  • Animals
  • Bone Marrow Cells / cytology
  • Carbon Tetrachloride / toxicity
  • Connective Tissue Growth Factor / metabolism
  • Disease Models, Animal
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Keratin-18 / genetics
  • Keratin-18 / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Rats
  • Spleen / pathology
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Actins
  • CCN2 protein, rat
  • Keratin-18
  • Transforming Growth Factor beta1
  • smooth muscle actin, rat
  • Connective Tissue Growth Factor
  • Hepatocyte Growth Factor
  • Carbon Tetrachloride