Bone Marrow-Derived Mesenchymal Stem Cell Potential Regression of Dysplasia Associating Experimental Liver Fibrosis in Albino Rats

Biomed Res Int. 2019 Nov 6:2019:5376165. doi: 10.1155/2019/5376165. eCollection 2019.

Abstract

Objectives: Assessing the therapeutic efficacy of superparamagnetic iron oxide nanoparticles (SPIO) labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) on experimental liver fibrosis and associated dysplasia.

Materials and methods: MSCs were obtained from 10 male Sprague-Dawley rats while 50 female rats were divided into control (CG), liver fibrosis (CCL4, intraperitoneal injection of CCl4 for 8 weeks), and CCL4 rats treated with SPIO-labeled MSCs (MSCs/CCl4) with and without continuing CCL4 injection for another 8 weeks. Assessment included liver histopathology, liver function tests, transmission electron microscopic tracing for homing of SPIO-MSCs, immunofluorescence histochemistry for fibrosis and dysplasia markers (transforming growth factor-beta (TGF-β1), proliferation nuclear antigen (PCNA), glypican 3)), and quantitative gene expression analysis for matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1).

Results: SPIO-labeled MSCs were engrafted in the fibrotic liver and the BM/MSCs demonstrated regression for fibrous tissue deposition and inhibition progression of dysplastic changes in the liver of CCl4-treated rats on both the histological and molecular levels.

Conclusion: BM-MSCs possess regenerative and antidysplastic potentials.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bone Marrow / metabolism
  • Bone Marrow / pathology*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Carbon Tetrachloride / pharmacology
  • Disease Models, Animal
  • Female
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / parasitology*
  • Liver Function Tests / methods
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Biomarkers
  • Transforming Growth Factor beta1
  • Carbon Tetrachloride