Bone marrow stromal/stem cell-derived extracellular vesicles promote bone regeneration in vivo

Emerging evidence suggests that extracellular vesicles (EVs) are secreted by diverse tissues and play important roles in cell-cell communication, organ interactions and tissue homeostasis. Studies have reported the use of EVs to stimulate tissue regeneration, such as hepatic cell regeneration, and to treat diseases, such as pulmonary hypertension. However, little is known about the osteogenic effect of EVs.

In this study, researchers from the Shanghai Jiao Tong University explore the role of bone marrow stromal cell-derived EVs in the regulation of osteoblast activity and bone regeneration. They isolated bone marrow stromal/stem cell (BMSC)-derived EVs through gradient ultracentrifugation and ultrafiltration, and tested the influence of the EVs on osteogenesis both in vivo and in vitro. The results indicated that EVs positively regulated osteogenic genes and osteoblastic differentiation but did not inhibit proliferation in vitro. Furthermore, the researchers constructed an EVs delivery system to stimulate bone formation in Sprague Dawley (SD) rats with calvarial defects. They found that BMSC-derived EVs led to more bone formation in the critical-size calvarial bone defects. Moreover, they found that miR-196a plays an essential role in the regulation of osteoblastic differentiation and the expression of osteogenic genes. The researchers anticipate that our assay using bone marrow stromal cell-derived EVs will become a valuable tool for promoting bone regeneration.

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(a) A representative electron microscopic image of EVs derived from BMSCs (White arrow). Scale bar, 200 nm. The western blot of EV-depleted medium and EVs pallet also demonstrated that BMSC-derived EVs were isolated. For the FACS analysis, EVs (open trace) and negative control (filled trace) are shown. (b) Confocal fluorescence analysis was performed 4 h after incubation. The EVs were PKH67-labeled according to the manufacturer’s protocol (green fluorescence). The endoplasmic reticulum, Golgi apparatus and lysosomes were stained by ER-Tracker Red, Golgi-RFP and Lyso-Tracker Red. DAPI was used to stain the cell nuclei (blue fluorescence). Red arrows showed shallow green round-like staining indicating that the foreign EVs were degraded. The white arrow showed the round Golgi apparatus lumen.

Qin Y, Wang L, Gao Z, Chen G, Zhang C. (2016) Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Scientific Reports 6(21961). [article]

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