Abstract

Abstract Mesenchymal stem cell (MSC)-based gene therapy is a promising tool for the treatment of various neurological disease including brain tumor. The tumor necrosis factor-related apoptotic ligand (TRAIL) is believed to have promise as a cancer the therapy. For stem cell therapy in the brain tumor, therapy efficiency of stem cells by non-invasive method is extremely limited due to blood brain barrier (BBB). Noninvasive pulsed focused ultrasound (FUS) can temporarily opening the BBB of specific areas in the brain. Herein, we investigated the tumor-targeted BBB temporarily opening by FUS and therapeutic efficiency of NIR fluorescence-labeled MSCs-TRAIL by intravenous injection in brain tumor. In addition, we observed the inflammatory changes of microglia cells by FUS using PET-CT and histological analysis. As a results, In vivo survival experiments showed that FUS treated-MSC-TRAIL group has greater therapeutic efficacy than FUS untreated-groups. The number of MSCs accumulated specifically site in the tumor region. MSC migration toward FUS treated-tumor site greater compared to the FUS untreated-tumors. Furthermore, the changes of microglia activity by FUS was no difference between the other groups. Collectively, these results suggest that therapeutic efficacy of MSC-TRAIL increases by temporarily opening the BBB using the FUS, which may be a more useful strategy for cancer therapy.

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