Gene therapy of rat intracranial glioma by Mesenchymal Stem Cells (MSCs) transfected with the beta-interferon gene

Abstract

Objective To investigate the gene therapy of experimental rat intracranial glioma by MSCs-hIFN-β. Methods Cellular viability of C6 glioma cell was assessed by MTT assay and the content of hIFN-β was analyzed using enzyme linked immunosorbent assay (ELISA). C6 glioma model was established and was verified by histopathological characteristics and MRI images. Clinical manifestation of the rat bearing C6 glioma were recorded. Direct intratumoral injection of MSCs-IFN-β gene was undertaken, survival of mices were recorded. The expression of protein of hIFN-β in C6 glioma tissure was examined immunohistochemically. Results MSCs transfected with IFN-β significantly inhibited the growth of C6 glioma cell even when the ratio of C6 to MSCs-IFN-β was 100: 1. There was a dose-dependent increase in the amount of soluble IFN-β that directly correlated with the inhibition of tumor cell growth. There was significant difference between the mean tumor volume of group MSCs-IFN-β and group saline, MSCs after 10 days. Compared with animals treated with saline or with MSCs, treated with MSCs-IFN-β resulted in a significant increase in animal survival (P ＜ 0. 0l ). Conclusion In vitro and in vivo efficacy studies show that MSCs can be engineered to release IFN-β and that these engineered MSCs can be exploited to therapeutic advantage against gliomas. Key words: MSCs; hIFN-β; Adenovirus; Gene therapy; Glioma