Development of new treatment for intractable inflammatory bowel disease using exosome derived from DFAT

• Project/Area Number: 17K17007
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Nihon University
• Principal Investigator: KAWASHIMA Hiroyuki 日本大学, 医学部, 助手 (60645703)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: DFAT / 炎症性腸疾患 / エクソソーム / 脱分化脂肪細胞 / Exosome / exosome / Tリンパ球 / 免疫抑制

Outline of Final Research Achievements

We extracted RNA from DFAT- and ASC-derived exosomes and analyzed miRNA expression.We confirmed the expression of miRNAs that regulate T cell proliferation. and we also confirmed the expression of miRNAs that differentiation of naive T cells to regulatory T cells, or differentiation of Th17 cells.
We examined the effect of exosomes derived from DFAT and ASC on proliferation and differentiation of human T cells.It was confirmed that both of them suppressed the proliferation of T cells ,promoted the differentiation into regulatory T cells, and suppressed the differentiation into Th17 cells in a dose-dependent manner.

Academic Significance and Societal Importance of the Research Achievements

我々は脂肪を脱分化して作製した脱分化脂肪細胞(DFAT)が、間葉系幹細胞と同様の免疫抑制能をもつことを示し、炎症性腸疾患を念頭に新規治療法の開発を行ってきた。しかしDFATを静脈投与することで、炎症性腸疾患の改善は見られたものの、投与した細胞の大半は肺でトラップされ、target部位への細胞輸送はわずかとなってしまうだけでなく、しばしば肺塞栓によって呼吸停止を引き起こすこともあった。今回DFATの免疫抑制能の一部が、exosomeによりもたらされることが証明されたことで、今後細胞を直接使用せずにエクソソーム単体で炎症性腸疾患に対する新規治療法を開発することが期待される。