Combination therapy for gliomas using temozolomide and interferon-beta secreting human bone marrow derived mesenchymal stem cells

Abstract

Objective : Malignant gliomas are the most common primary tumors of the central nervous system and the prognosis of patients with gliomas is poor. The combination of interferon-bata (IFN-ß) and temozolomide (TMZ) has shown significant additive antitumor effects in human glioma xenograft models. Considering that the poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor, the tropism of human bone marrow-derived mesenchymal stem cells (MSC) for malignant gliomas can be exploited to therapeutic advantages. We investigated the combination effects of TMZ and MSCs that secrete IFN-ß on gliomas. Methods : We engineered human MSCs to secret mouse IFN-ß (MSC-IFN-ß) via adenoviral transduction and confirmed their secretory capacity using enzyme-linked immunosorbent assays. In vitro and in vivo experiments were performed to determine the effects of the combined TMZ and MSCIFN-ß treatment. Results : In vitro, the combination of MSC-IFN-ß and TMZ showed significantly enhanced antitumor effects in GL26 mouse glioma cells. In vivo, the combined MSC-IFN-ß and TMZ therapy significantly reduced the tumor size and improved the survival rates compared to each treatment alone. Conclusion : These results suggest that MSCs can be used as an effective delivery vehicle so that the combination of MSC-IFN-ß and TMZ could be considered as a new option for the treatment of malignant gliomas.