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

Asian Pac J Cancer Prev. 2018 Jun 25;19(6):1627-1631. doi: 10.22034/APJCP.2018.19.6.1627.

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.

Keywords: Hepatocellular carcinoma; sorafenib; human placenta Mesenchymal stem cell; animal model.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Proliferation
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Green Fluorescent Proteins