“双靶向”应用机械应力条件下人脐血MSCs来源外泌体对牵张成骨的作用及其可能机制

本项目针对牵张成骨（DO）治疗所面临的临床难题及干细胞外泌体（Exos）治疗目前的瓶颈问题，提出了新的研究思路：首先，运用机械应力（MS）刺激人脐血干细胞（HucMSCs）获得MS-Exos，通过增强HucMSCs的旁分泌效应来提高其外泌体的生物学活性和功能；然后，构建对外泌体具有高亲和力、高特异性的DNA水凝胶，实现MS-Exos的高效富集和无伤分离，进而最大可能地保留MS-Exos的治疗效力；最后，将提取出来的MS-Exos与BMMSCs特异性的aptamer连接，进而将MS-Exos靶向递送至DO区域内的BMMSCs中，最终在DO过程中实现MS-Exos的骨靶向治疗。综上所述，本项目这一靶向Exos分离和靶向Exos治疗的“双靶向”研究方案，不仅会为临床DO的精准治疗提供新的策略，还将为干细胞Exos治疗在骨组织再生领域的应用揭开新的序幕。

Regarding the clinical problems of distraction osteogenic (DO) treatment and the current bottleneck ofstem cell-derived exosomes (Exos) therapy, this project puts forward a new research plan. First, mechanical stress (MS) is used to stimulate human umbilical cord blood stem cell (HucMSCs) to obtian the MS-Exos with increased biological activity and function by enhancing the paracrine effect of HucMSCs. Then, a DNA hydrogel with high affinity and high specificity for Exos is constructed to achieve efficient enrichment and non-invasive separation of MS-Exos, which will retain the therapeutic efficacy of MS-Exos as much as possible. Last, the extracted MS-Exos is connected with BMMSCs-specific aptamer, and then the MS-Exos-aptamer complex is targetedly delivered to the BMMSCs in the distraction gap, and thus the bone-targeted therapy of MS-Exos is achieved in the process of DO. To sum up, the double targeting application of MS-Exos will not only provide a new strategy for clinical accurate DO treatment, but also open a new prelude for the application of stem cell Exos therapy in the field of bone regeneration.