Aptamer-functionalized Exosomes from Bone Marrow Stromal Cells Target Bone to Promote Bone Regeneration
In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem/stromal cells (BMSCs/STs) for compensation of bone resorption by osteoclasts is a major reason of osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cells-derived exosomes (STExo) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro. However, intravenous injection of STExo is inefficient to ameliorate osteoporotic phenotypes in ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which maybe because STExo are predominantly accumulated in liver and lung, but not bone. Hereby, STExo surface is conjugated with a BMSCs/STs-specific aptamer, which delivers STExo into BMSCs/STs within bone marrow. Intravenous injection of STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSCs/STs-specific aptamer-functionalized STExo to target bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.