Exosomes Enhance Adhesion and Osteogenic Differentiation of Initial Bone Marrow Stem Cells on Titanium Surfaces

Abstract

Successful osseointegration involves the biological behavior of bone marrow stem cells (BMSCs) on an implant surface; however, the role of BMSC-derived extracellular vesicles (EVs)/exosomes in osseointegration is little known. This study aimed to: (i) explore the interaction force between exosomes (Exo) and cells on a titanium surface; (ii) discuss whether the morphology and biological behavior of BMSCs are affected by exosomes; and (iii) preliminarily investigate the mechanism by which exosomes regulate cells on Ti surface. Exosomes secreted by rat BMSCs were collected by ultracentrifugation and analyzed using transmission electron microscopy and nanoparticle tracking analysis. Confocal fluorescence microscopy, scanning electron microscopy, Cell Counting Kit-8 (CCK-8), quantitative real-time polymerase chain reaction techniques, and alkaline phosphatase bioactivity, Alizarin Red staining, and quantification were used to investigate the exosomes that adhere to the Ti plates under different treatments as well as the morphological change, adhesion, spread, and differentiation of BMSCs. We found that exosomes were efficiently internalized and could regulate cell morphology and promoted the adhesion, spreading, and osteogenic differentiation of BMSCs. These were achieved partly by activating the RhoA/ROCK signaling pathway. Our discovery presents a new insight into the positive regulatory effect of exosomes on the biological behaviors of BMSCs on Ti surface and provides a novel route to modify the surface of a Ti implant.

Properties improvement of titanium alloys scaffolds in bone tissue engineering: a literature review

“…Cell and animal experiments showed that this cell-free scaffold could efficiently regenerate bone tissue, which presents a novel bone regeneration method. Lan et al (88) reported a similar result further explained the mechanism that this osteogenic induction was achieved partly by activating the RhoA/ROCK signaling pathway.…”

Influence of Periodontal Ligament Stem Cell-Derived Conditioned Medium on Osteoblasts

“…It is, however, for OP and BSP. These results indicate that osteogenesis is not complete at 72 h. Lan et al demonstrated that the increase in ALP and OCN expression occurred only after 6 days of contact with a medium containing exosomes [62]. In their study, Jin et al observed an increase in ALP expression after 10 days of coculture with MSC-CM [60].…”

Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis

“…BMSC-EVs are useful in bone regeneration for overcoming issues such as inflammation, lower seeding efficiency, and immune response of cell transplantation, as well as enabling fast release and rapid concentration decay of growth factors [ 50 , 52 , 53 ]. Based on our previous findings [ 46 ], we further investigated the osteogenic capacity of EVs derived from Nell1 -modified BMSCs and determined how Nell1 -induced differentiation was coordinated with EV-miRNA changes. We isolated EVs from Nell1- modified BMSCs and demonstrated that modified EVs were able to induce BMSC osteogenesis in vitro and repaired bone defects in vivo .…”

“…We hypothesized that Nell1 modification could induce a series of changes in BMSCs as well as EVs. Based on the results of our previous study, which verified the osteo-inductive capacity of BMSC-EVs on the titanium surface of dental implants [ 46 ], we examined whether EVs secreted from Nell1 -modified BMSCs ( Nell1 /EVs) could induce osteogenesis in vitro and acellular bone regeneration in vivo ( Fig. 1 ).…”