Anti-inflammatory effect of mesenchymal stem cells on hepatocellular carcinoma in the xenograft mice model

Vet Med Sci. 2022 Sep;8(5):2086-2091. doi: 10.1002/vms3.886. Epub 2022 Jul 15.

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Sorafenib is the standard treatment used in the advanced stages of HCC. Cell therapy with mesenchymal stem cells (MSCs)-based cell therapy has proven effective in immune regulation and tumour growth inhibition.

Objectives: In this study, we investigated the anti-inflammatory effect of MSCs on HCC xenografts.

Methods: Human HepG2 cell lines were subcutaneously implanted into the flank of 12 nude mice, divided into three groups: the control group, the IV group (intravenous MSCs injection) and the local group (local MSCs injection). Mice were sacrificed 6 weeks after tumour implantation, and tumours were resected entirety. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the gene expression of inflammatory markers, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1α and IL-10. Aspartate transaminase (AST), alanine transaminase (ALT) and urea levels were measured using spectrophotometry to ensure the safety of MSC therapy.

Results: Gene expressions for all three inflammatory markers were reduced in both MSCs groups compared to the control group. AST, ALT and urea levels remained in normal ranges.

Conclusions: MSC therapy can reduce inflammation in HCC xenograft mouse models.

Keywords: hepatocellular carcinoma; human placenta; inflammation; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Alanine Transaminase / pharmacology
  • Alanine Transaminase / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Aspartate Aminotransferases / metabolism
  • Aspartate Aminotransferases / pharmacology
  • Aspartate Aminotransferases / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / veterinary
  • Disease Models, Animal
  • Heterografts
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-10 / pharmacology
  • Interleukin-10 / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / veterinary
  • Mesenchymal Stem Cell Transplantation* / veterinary
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Nude
  • Sorafenib / metabolism
  • Sorafenib / pharmacology
  • Sorafenib / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Sorafenib
  • Aspartate Aminotransferases
  • Alanine Transaminase