Development of novel extracellular vesicle (EV)/exosome-based treatment for multiple myeloma: therapeutic potential of miR125b-containing osteoblast-derived EVs

Description

EVs are of interest as cell-to-cell communicators that transport microRNAs (miRs) to target cells. Mature osteoblasts (OBs) have been reported to produce anti-myeloma (MM) activity in contrast to their precursors, bone marrow stromal cells/mesenchymal stem cells. We found the critical role of OB-derived EVs (OB-EVs) in induction of MM cell death without impairing normal hematopoietic cells. In this project, we aim to clarify the uniqueness of OB-EVs in MOAs for induction of MM cell death, focusing on miR-125b abundantly contained in the EVs. We will highlight their potential to alter the phosphorylation status and metabolisms unique for MM cells, posing the OB-EVs as a safe and novel option of treatment for patients with RRMM with functional high risk and even for super-elderly/frail patients. We will also develop a novel OB differentiation-culture system to efficiently produce a large amount of highly active OB-EVs using human osteoblastic cell lines with selective bone anabolic agents and establish a large-scale collection system of the EVs with high purity for future clinical application.