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Luo, Zhong-Wei; Li, Fu-Xing-Zi; Liu, Yi-Wei; Rao, Shan-Shan; Yin, Hao; Huang, Jie; Chen, Chun-Yuan; Hu, Yin; Zhang, Yan; Tan, Yi-Juan; Yuan, Ling-Qing; Chen, Tuan-Hui; Liu, Hao-Ming; Cao, Jia; Liu, Zheng-Zhao; Wang, Zhen-Xing; Xie, Hui
Nanoscale, 11/2019, Volume: 11, Issue: 43Journal Article
In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro . However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the 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 BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture. A novel strategy to deliver therapeutic exosomes to bone is developed for the first time by conjugating a specific BMSC-targeting aptamer to the exosomal surface.
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