GENE THERAPY USING IL-24-EXPRESSING UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS AGAINST GLIOMA

Abstract Despite many advances have been made in treatment of gliomas, patients prognosis remains poor. Stem cell-based therapy has been thought to be a promising option for gliomas and many studies have reported that umbilical cord-derived mesenchymal stem cells (UC-MSCs) are ideal gene vectors for tumor gene therapy. Interleukin 24 (IL-24) is a pleiotropic immunoregulatory cytokine which has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. However, there are still some challenges in its clinical application, such as the half-life, toxicity caused by high-dose application, and so on. Therefore, we hypothesize that combination of gene transfer with stem cell transplantation could overcome the problems. In this study, we investigated UC-MSCs transduced with lentiviral vectors carrying IL-24 complementary DNA as a vehicle for the targeted delivery of IL-24 to local tumor sites. The engineered UC-MSCs selectively migrated to glioma cells and showed the antitumor effect in vitro and in vivo. The restrictive efficacy of these UC-MSCs was related to the inhibition of proliferation and induction of apoptosis in tumor cells. These findings indicate that UC-MSCs-based IL-24 gene therapy can obviously suppress the growth of glioma xenografts, thereby suggesting the potential for future therapeutic interventions in the treatment of gliomas. Keywords: Glioma, Gene therapy, Umbilical cord-derived mesenchymal stem cells (UC-MSCs), Interleukin 24 (IL-24)