The Tumour-Suppressive Role of miRNA-Loaded MSC-Derived Extracellular Vesicles in Osteosarcoma: A Systematic Review and Meta-Analysis

Osteosarcoma (OS) is a malignant bone tumour that mostly affects adolescents. Although conventional treatment approaches improved disease prognosis significantly, high metastasis rate and recurrence impose a substantial disease burden on patients. Therefore, innovation of targeted therapy is of pressing importance towards better disease prognosis. Several in vitro studies using microRNA delivered via mesenchymal stem cell-derived extracellular vesicles presented significant results in reducing OS metastatic properties. Henceforth, the objective of this study, which is to compile and analyse data from relevant studies, subsequently provides a comprehensive and evidence-based summary that validates the tumour-suppressive role of miRNA-loaded MSC-derived EVs targeting OS metastasis. Studies were systematically selected from three databases: PubMed, Web of Science and Scopus, according to the PRISMA criteria and flowchart. Experimental data regarding proliferation, apoptosis, migration and invasion were extracted using WebPlotDigitizer and analysed using the Comprehensive Meta-Analysis (CMA) software. A systematic search from databases identified 33 studies, with four studies fulfilling the inclusion and exclusion criteria after final screening process. The pooled meta-analysis demonstrated that miRNA-loaded MSC-derived EVs were associated with a significant decrease in proliferation, migration and invasion rates of the OS cells, with a significant increase in apoptosis rate. Moreover, low to moderate heterogeneity was observed across selected studies. This review confirms that miRNA-loaded MSC-derived EVs significantly suppressed OS metastasis by inhibiting proliferation, migration and invasion while promoting apoptosis. However, clinical translation is currently limited by the lack of standardised protocols necessary for large-scale trials to validate EV-based therapies as a potential therapeutic approach in the future.