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Characterization and Validation of Hepatocellular Carcinoma (Hcc) Xenograft Tumor As a Suitable Liver Cancer Model for Preclinical Mesenchymal Stem Cell Studies Publisher Pubmed



Hajighasemlou S1, 2 ; Pakzad S2 ; Ai J1 ; Muhammadnejad S3 ; Mirmoghtadaei M4 ; Hosseinzadeh F1 ; Gharibzadeh S5 ; Kamali A6 ; Ahmadi A7 ; Verdi J1
Authors
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Authors Affiliations
  1. 1. Tissue Engineering and Applied Cell Sciences, Tehran University of Medical Science, Pasteur Institute of Iran, Iran
  2. 2. Iran Ministry of Health and Medical Education, Food and Drug Control Laboratory (FDCL), Pasteur Institute of Iran, Iran
  3. 3. Cancer Biology Research Center Tehran, Tehran University of Medical Science, Pasteur Institute of Iran, Iran
  4. 4. Tehran University of Medical Sciences (TUMS), Pasteur Institute of Iran, Iran
  5. 5. Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Iran
  6. 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. 7. School of Advanced Technologies in Medicine, Tehran University of Medical Science, Pasteur Institute of Iran, Iran

Source: Asian Pacific Journal of Cancer Prevention Published:2018


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. © 2018, Asian Pacific Organization for Cancer Prevention.