Therapeutic Role of Bone Marrow-Derived Mesenchymal Stem Cells in Controlling Prognosis of Hepatocellular Carcinoma in a Murine Model.

Abstract

Hepatocellular carcinoma is the fourth leading cause of cancer deaths in the world. Conven - tional methods of cancer therapy are either invasive or have undesirable side effects. Therefore, exploring new therapeutic strategies to control the progression of hepatocellular carcinoma, such as cell-based therapies, is a key issue for prolonging patient survival. In this study, we aimed to evaluate tumor suppressive effects of mesenchymal stem cells on the in vivo pro - gression of hepatocellular carcinoma in murine model. Hepatocellular carcinoma was induced in 40 rats with diethylnitrosamine. Rats were divided into 4 groups: 1 group injected with diethylnitrosamine only, 1 group injected with diethylnitrosamine and 1 dose of rat bone marrowderived mesenchymal stem cells, 1 group injected with diethylnitrosamine and 2 doses of rat bone marrowderived mesenchymal stem cells, and 1 group was injected with diethylnitrosamine and 3 doses of rat bone marrow-derived mesenchymal stem cells. Rats were killed after 1 month of dose 3. Liver specimens were histopathologically examined, and serum samples were examined for liver function and cytokines. Histopathological examination revealed that mesenchymal stem cell transplant induced liver regeneration. It also improved liver function as revealed by decreased levels of alanine and aspartate aminotransferase. Mesenchymal stem cells also repaired the immunopathology of the liver environment, as it decreased levels of interleukin 2 and 10, tumor necrosis factor α, and interferon γ. Mesenchymal stem cell infusion significantly enhanced hepatic structure and function of livers in a rat hepatocellular carcinoma model.