Development of anti-invasion therapy in glioblastoma multiforme using MSC transfected with microRNA

• Project/Area Number: 26293325
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyushu University
• Principal Investigator: Akira Nakamizo 九州大学, 医学(系)研究科(研究院), 研究員 (80529800)
• Co-Investigator(Kenkyū-buntansha): 溝口 昌弘 九州大学, 医学(系)研究科(研究院), 研究員 (50380621) ; 吉本 幸司 九州大学, 大学病院, 講師 (70444784) ; 天野 敏之 九州大学, 医学(系)研究科(研究院), 研究員 (70448413) ; 飯原 弘二 九州大学, 医学(系)研究科(研究院), 教授 (90270727)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: microRNA / 間葉系幹細胞 / 神経膠芽腫 / 脳神経疾患 / miRNA / 悪性脳腫瘍 / micro RNA / exosome

Outline of Final Research Achievements

Human bone marrow derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may be useful as a vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRs) have been shown to suppress the invasiveness of malignant gliomas. The purpose of this study is to test the potential to become vehicles for delivery of miRs to malignant gliomas. The invasion of U87 cells co-cultured with hMSCs co-transfected with hsa-miR-145 and 31-5p was reduced to 60.7% of the control without affecting the tropism of hMSCs for U87 cells in a matrigel invasion assay. When U87 cells were co-implanted into the striatum of organotypic brain slices with hMSCs that were co-transfected with hsa-miR-145 and 31-5p, the relative invasive area was decreased by 37.1%. Our results suggest that hMSCs are applicable as a delivery vehicle for miRs.