Adipose mesenchymal stem cell-based therapy: Anticancer molecular mechanisms in hepatoma model and bone marrow

Background : Adipose-derived mesenchymal stem cells (AD-MSCs) can be used as therapeutic agents for the treatment of patients with HCC Aim: The study aimed to establish an animal model for hepatocellular carcinoma (HCC) by using diethyl nitrosamine (DEN) and carbon tetrachloride (CCl 4 ) in a short time. Materials and Methods: Forty-five female rats were subdivided into three groups: control (G1), HCC model (G2), and therapeutic (G3). Each rat in the G2 groups was injected with DEN and after 1 week was injected again with CCl 4 , whereas G3 rats were injected with AD-MSCs immediately after the tumor appeared. Results: The injection of DEN/CCl 4 was correlated with the increase in alanine transaminase, aspartate aminotransferase, and alpha-fetoprotein levels. Also, it caused oxidative stress as indicated by an increase in nuclear factor-erythroid factor 2-related factor-2 (Nrf2), vascular endothelial growth factor levels, and fibrosis. However, BCL2-associated X protein (BAX) was decreased. Transplantation of AD-MSCs induced apoptosis by increasing BAX and decreasing Nrf2 levels, which significantly inhibited angiogenesis. Histologically, our results indicated that AD-MSCs alleviated hepatocellular carcinoma, fibrosis, and nuclear morphology. Additionally, the bone marrow (BM) maturation index ratio parameter was restored to a normal stage. Conclusion: AD-MSCs have a wide range of targeted anticarcinogenic properties and can regenerate BM precursors of cellularity.