Secreted TRAIL gene-modified adipose-derived stem cells exhibited potent tumor-suppressive effect in hepatocellular carcinoma cells

Objective: Considering the potential of adipose-derived stem cells (ADSCs) migrating towards cancer cells, this study was performed to explore the function of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) modified ADSCs on the development and progression of hepatocellular carcinoma (HCC).

Methods: ADSCs were extracted from human adipose tissues and identified through immunofluorescence and flow cytometry. Oil red staining and alizarin red staining were performed to clarify the differentiation potential of ADSCs. AAV-CMV-sTRAIL was transfected into ADSCs before Western blot and Transwell measurements. sTRAIL-ADSCs were cocultured with HCC cells to explore its effect on the proliferation and apoptosis of HCC cells. The possible effect of sTRAIL-ADSCs or ADSCs on tumor growth and metastasis was determined in vivo using xenograft nude mouse models.

Results: ADSCs were successfully extracted from adipose tissues, which were confirmed by cell morphology and positive expressions of CD44 and CD105. ADSCs were found with differentiation potential. After transfection, TRAIL was stably expressed in sTRAIL-ADSCs. Both ADSCs and sTRAIL-ADSCs can migrate towards HCC cells. In addition, sTRAIL-ADSCs can promote the cell apoptosis and inhibit cell proliferation in vitro, on parallel it can also suppress epithelial-mesenchymal transition, tumor growth, and metastasis in vivo.

Conclusion: TRAIL modified ADSCs can migrate towards HCC cells to inhibit tumor growth and the metastasis of implanted HCC tumors, which hints TRAIL modified ADSCs may be a new therapeutic approach for HCC treatment.