Novel therapies development of multiple myeloma using engineering exosomes derived from bone marrow stromal cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07183
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Tokyo Medical University
• Principal Investigator: Ohyashiki Junko 東京医科大学, 医学部, 教授 (20191950)
• Co-Investigator(Kenkyū-buntansha): 梅津 知宏 東京医科大学, 医学部, 講師 (40385547)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: エクソソーム / 骨髄間質細胞 / 多発性骨髄腫 / 腫瘍血管新生 / miRNA

Outline of Final Research Achievements

Bone marrow stromal cells (BMSCs) and their exosomes are a promising area of cancer therapy. Here, we investigated therapeutic effects of BMSC exosomes derived from young and elderly donors using in vivo models of bone marrow in multiple myeloma (MM). We found that the donor’s age decides senescent changes in BMSC, and exosomes derived from young BMSCs could block MM cell-induced angiogenesis in Matrigel plug. We also noted young BMSC-specific exosomal miRNA, such as miR-340. Of note is that the anti-angiogenic effect was potentiated by engineering exosomes of elderly BMSCs; exosomes are directly transfected with miR-340, resulting in exosome rejuvenation.
Our results suggest that the BMSC exosomes is able to transfer the miRNAs, which have the ability to inhibit angiogenesis and progression of MM. The present study provides a new insight toward exosome-based cancer therapy by engineering exosomes of BMSCs.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫の骨髄微小環境制御を主眼としたアプローチはSDF-1やCXCR4などの液性因子を中心に展開されている。本研究では人工的にmiRNAを直接エクソソームに添加し効果を発揮させるという我々が開発した革新的手法を用いている。また、抗原性が少なく細胞治療としての有用性が検証されているMSCに着眼し、細胞治療の発展型ともいえる核酸医薬研究である。抗腫瘍血管新生効果の高い「機能強化型エクソソーム」を安定的に供給する事も可能になる。本研究は技術的にも革新的がん治療として注目の領域であると同時に高齢化社会でますます患者数の増加が見込まれる多発性骨髄腫患者のADL向上につながり社会的貢献度は大きい。