ABSTRACT
Homing and tumor attenuation potential of BM-MSCs labelled with superparamagnetic iron-oxide nanoparticles (SPIONs) in a rat model of hepatic cirrhosis was evaluated. Rat BM-MSCs were derived, characterized and labelled with SPIONs (200 nm; 25 mg Fe/ml). Hepatic cirrhosis was induced in Wistar rats (n=30; 10/group) with carbon tetrachloride (CCl4; 0.3 mL/kg body weight) injected twice a week for 12 weeks. Group-I was administered vehicle (castor-oil) alone; Group-II received two doses of unlabelled BM-MSCs (3x106 cells) and Group-III received two doses of SPIONs labelled BM-MSCs (3x106 cells) via tail vein injection (0.5 ml) at weekly intervals. All animals were sacrificed after two weeks for histological, radiological and biochemical analysis. Derived BM-MSCs demonstrated MSCs related CD markers. Histology confirmed induction of hepatic cirrhosis with CCL4. Levels of alanine-aminotransferase, aspartate-aminotransferase,alkaline-phosphatase and gamma glutamyl-transferase returned to normal levels following treatment with BM-MSCs. Uptake and homing of SPIONs labelled BM-MSCs, and reduction in the size of cirrhotic nodules were confirmed using transmission electron microscopy and magnetic resonance imaging respectively. BM-MSCs reduced the pathological effects of CCL4 induced hepatic cirrhosis and labelling BMMSCs with SPIONs were non-toxic and enabled efficient tracking using non-invasive methods.
ABSTRACT
BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) are reported to improve hepatic fibrosis, and may impact the signaling mechanisms leading to the induction of hepatocellular carcinoma (HCC) in animal models of liver cirrhosis. OBJECTIVES: The aim of this study was to clarify and explain the therapeutic role played by MSCs in hepatic cirrhosis and HCC by tracking them using nanoparticles. MATERIAL AND METHODS: Liver cirrhosis and HCC were established in rats with the use of carbon tetrachloride and diethylnitrosamine injection. Magnetic resonance imaging (MRI) was used to track nanoparticlelabeled MSCs in the intact animal following injection and to monitor the changes in the hepatic parenchyma. RESULTS: Labeling of MSCs with iron oxide nanoparticles did not adversely affect their viability and proliferation. MRI indicated a significant reduction in tumor mass in the labeled MSCs group compared to the control group. Histopathologic examination of the liver, following MSCs treatment, showed an apparently normal looking liver with no evidence of neoplastic cellular changes. The biochemical results support these findings. CONCLUSIONS: This work documents that MSCs could be labeled with nanoparticles and traced in normal and cirrhotic liver and in liver with HCC in animals using MRI. MRI monitors the homing and localization of MSCs in the liver. MSCs infusion in animal models of cirrhosis and carcinoma may prove to be useful in limiting the cirrhotic process. Also, it may have a possible therapeutic potential on the carcinogenic process.
