Characterization and Validation of Hepatocellular Carcinoma (HCC) Xenograft tumor as a Suitable Liver Cancer Model for Preclinical Mesenchymal Stem Cell Studies

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer and the third leading cause<br />of cancer-related death. sorafenib is used as a standard therapy to treat HCC. mesenchymal stromal cells (MSCs)<br />have also been used to suppress HCC. Here we investigate the development of a xenograft model of liver cancer to<br />study the homing of hpMSC-GFP cells, tumor kinetics and molecular characterizations of HCC. Methods: To create<br />xenograft models of HCC, HepG2 cell lines were inoculated into the flanks of 9 nude mice bilaterally. Animals were<br />then divided into three groups: the first group received hpMSC-GFP systemically, the second received intra-tumoral<br />hpMSC-GFP and the third received PBS. The first two groups were sacrificed after 72 hours of MSCs injection but<br />the third group was followed up for forty days. One tumor from each animal was then transferred to formalin buffer<br />for H&E staining and immunohistochemistry analysis (KI67 and CD34), and the other tumor was used for ex-vivo<br />imaging. Blood samples were taken from all subjects before sacrificing them. Results: Histopathological fidelity of<br />heterotopic HePG2 xenograft models to human HCC tumors was demonstrated. Biochemical evaluation suggested<br />the health of the animal's liver and kidneys. Ex-vivo imaging illustrated homing of more hpMSC-GFP cells in tumor<br />tissues derived from the group receiving intra-tumoral hpMSC-GFP. Conclusion: A standard method was used to<br />inoculate tumor cells and the intervention was shown to be safe to liver and kidneys. Local injection of MSCs can be<br />used as cell therapy to fight neoplasms.