Comparison Study of Stem Cell-Derived Extracellular Vesicles for Enhanced Osteogenic Differentiation

Impact statement Bone tissue engineering approaches aim to overcome current challenges associated with autologous bone grafts by delivering a combination of scaffolding material, cells, and bioactive factors to enhance bone regeneration. Extracellular vesicles (EVs) from bone marrow-derived mesenchymal stem cells (BMSCs) have recently been shown to enhance osteogenic differentiation and improve bone mineral deposition. Herein, EVs derived from placental stem cells (PSCs) have a comparative ability to improve osteogenic capability. PSCs have advantages such as higher proliferation capacity, the ability to be harvested without an invasive procedure, and they produce larger amounts of EVs. The feasibility of using these EVs will be especially important in clinical translational studies, which require substantial amounts of EVs to achieve this effect. Stem cell-derived extracellular vesicles (EVs) have shown great promise in the field of regenerative medicine and tissue engineering. Recently, human bone marrow-derived mesenchymal stem cell (BMSC)-derived EVs have been considered for bone tissue engineering applications. In this study, we evaluated the osteogenic capability of placental stem cell (PSC)-derived EVs and compared them to the well-characterized BMSC-derived EVs. EVs were extracted from three designated time points (0, 7, and 21 days) after osteogenic differentiation. The results showed that the PSC-derived EVs had much higher protein and lipid concentrations than EVs derived from BMSCs. The extracted EVs were characterized by observing their morphology and size distribution before utilizing next-generation sequencing to determine their microRNA (miRNA) profiles. A total of 306 miRNAs within the EVs were identified, of which 64 were significantly expressed in PSC-derived EVs that related to osteogenic differentiation. In vitro osteogenic differentiation study indicated the late-stage (21-day extracted)-derived EVs higher osteogenic enhancing capability when compared with the early stage-derived EVs. We demonstrated that EVs derived from PSCs could be a new source of EVs for bone tissue engineering applications.