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

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 CCl(4) for 8 weeks), and CCL(4) rats treated with SPIO-labeled MSCs (MSCs/CCl(4)) with and without continuing CCL(4) 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 CCl(4)-treated rats on both the histological and molecular levels. CONCLUSION: BM-MSCs possess regenerative and antidysplastic potentials.