Mesenchymal stromal cell-derived extracellular vesicles for bone regeneration therapy

Abstract

Purpose: To analyze preclinical bone regeneration studies employing mesenchymal stromal cell (MSC)- derived extracellular vesicles (EVs) and highlight any commonalities in EV biomarker expression, miRNA cargo(s) or pathway activation that will aid in understanding the underlying therapeutic mechanisms.

Methods: Articles employing EVs derived from either MSCs or MSC-like osteogenic stromal cells in preclinical bone regeneration studies are included in this review.

Results: EVs derived from a variety of MSC types were able to successfully induce bone formation in preclinical models. Many studies failed to perform in-depth EV characterization. The studies with detailed EV characterization data report very different miRNA cargos, even in EVs isolated from the same species and cell types. Few preclinical studies have analyzed the underlying mechanisms of MSC-EV therapeutic action.

Conclusion: There is a critical need for mechanistic preclinical studies with thorough EV characterization to determine the best therapeutic MSC-EV source for bone regeneration therapies. Issues including controlled EV delivery, large scale production, and proper storage also need to be addressed before EV-based bone regeneration therapies can be translated for clinical bone repair.

Keywords: Biomaterials; Bone regeneration; Extracellular vesicles; Mesenchymal stromal cells; Tissue engineering; miRNA.

Fig. 1

Overview of common marker (green hexagons) and miRNA (orange hexagons) cargos carried by EVs derived from different MSC and MSC-like cell sources that demonstrated osteogenic potential in preclinical animal models.

Fig. 2

Literature search results and screening process, based on PRISMA guidelines.