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

Document Type: Research Articles

Authors

1 Tissue Engineering and Applied Cell Sciences, Tehran University of Medical Science, Tehran, Iran.

2 Iran Ministry of Health and Medical Education, Food and Drug Control Laboratory (FDCL), Tehran, Iran.

3 Cancer Biology Research Center Tehran, Tehran University of Medical Sciences, Tehran, Iran.

4 Tehran University of Medical Sciences, (TUMS),Tehran, Iran.

5 Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran.

6 Department of Stem Cells and Developmental Biology, Cell Science and Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

7 School of Advanced Technologies in Medicine, Tehran University of Medical Science,, tehran, Iran.

Abstract

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

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