Mesenchymal stem cell therapy of hepatocellular carcinoma in rats: Detection of cell homing and tumor mass by magnetic resonance imaging using iron oxide nanoparticles

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 nanoparticle-labeled 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.