Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

Abstract

Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.

No Effect on Tumorigenesis in MG63 Cells Induced by Co-Cultured Mesenchymal Stem Cells

“…In the TME, the effect of MSCs on tumor cells is largely dependent on the cytokines secreted by MSCs. Studies have shown that these cytokines can stimulate tumor cells leading to tumor development and metastasis by promoting migration and immune escape [ 20 , 21 ]. In osteosarcoma cells, cytokine release is considered as a biomarker of tumor progression [ 22 , 23 ].…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…Recent studies have shown that EVs secreted by MSCs have similar therapeutic effects on MSCs because some of the paracrine effects of MSCs are derived from exosomes, and most of the therapeutic effects of MSCs are responsible for the paracrine effects of EVs in certain diseases via miRNAs, mRNAs, and proteins as functional molecules [ 212 , 213 , 214 , 215 ].…”

Delineating the role of extracellular vesicles in cancer metastasis: A comprehensive review

“…Futuristic line of cancer treatment focusing on tumor microenvironment with/using modified mesenchymal stem cells. miRNA profiling from circulating sEVs is equivalent to sEVs profiling from tissue (170)(171)(172). Tumor-derived sEVs in the peripheral circulation exhibit different miRNA expression patterns than healthy person sEVs.…”