Exosomes from human urine-derived stem cells ameliorate particulate polyethylene-induced osteolysis
Abstract Background: Wear particle-induced periprosthetic osteolysis is a common long-term complication of total joint arthroplasty, and represents the major cause of aseptic loosening and subsequent implant failure. Currently, there are no effective therapeutic options to prevent osteolysis from occurring and often need revision surgery. Exosomes are important nano-sized paracrine mediators of intercellular communications and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the therapeutic potential of exosomes from human urine-derived stem cells (USC-Exos) in preventing wear particle-induced osteolysis.Methods: USCs were characterized by flow cytometry and multiple differentiation potential. USC-Exos were identified by transmission electron microscopy (TEM), dynamic light scattering (DLS) and western blotting (WB). The impact of USC-Exos on osteoblastic differentiation of bone marrow mesenchymal stromal cells (BMSCs) and osteoclastogenesis of RAW264.7 cells were verified in vitro. The effects of USC-Exos on ultra high molecular weight PE (UHMWPE)-induced murine calvarial osteolysis model were tested to evaluate bone mass, inflammation, osteogenic and osteoclastic activities.Results: USCs were positive for CD44, CD73, CD29 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteogenic, chondrogenic, and adipogenic cells. USC-Exos exhibited a round-shaped morphology with a double-layered membrane structure and positive for CD63 and TSG101, negative for Calnexin. In vitro, USC-Exos could promote the osteogenic differentiation of BMSCs, reduces the production of proinflammatory factors in macrophages and suppresses their osteoclastic abilities. In vivo, injection of USC-Exos into the center of the calvariae caused less inflammatory cytokine generation and less osteolysis compared to control and significantly enhanced the bone formation.Conclusions: Our findings demonstrate that USC-Exos can prevent UHMWPE-induced osteolysis by inciting less inflammatory, inhibiting bone resorption and stimulating bone formation. USC-Exos may represent a potential natural agent for the treatment of periprosthetic osteolysis and to obtain therapeutic exosomes for osteolytic treatment, aseptic loosening patients may just need to collect a certain volume of their own urine to harvest USCs and USC-Exos.