短波红外荧光纳米探针示踪技术监测骨髓间充质干细胞在腱骨愈合中迁移机制的研究

Tendon-bone healing is a critical research topic in the field of sport medicine, and how to accelerate this process is still a great challenge. Currently, bone mesenchymal stem cells (BMSCs) therapy is treated as a promising solution, and has been widely studied in the world. However, the in vivo mechanism of BMSCs on Tendon-bone healings still unclear because there is no real-time results of their moving and distribution in the body. We have had successfully developed a novel in vivo shortwave infrared spectral imaging based on silver sulfide (Ag2S) quantum dots (QDs) in previous works. Herein, we will firstly use Ag2S QDs as a fluorescent reporter to conjugate with BMSCs in this project, and then real-time detection those in vivo details of BMSCs labelled by Ag2S QDs in the rabbit model of tendon-bone healing. Furthermore, this project will provides more reliable in vivo results, and the distribution pattern and underlying moving mechanism of BMSCs will also be further analyzed based on those results. In a word, this project will not only provides more reliable evidences for BMSCs therapy on tendon-bone healing, but also pave a novel technology for further studying tendon-bone healing in future.

腱骨愈合是运动医学领域的重要研究内容，目前采用骨髓间充质干细胞(Bone Mesenchymal Stem Cells，BMSCs)促进腱骨愈合的研究结果令人鼓舞。但是对于BMSCs在腱骨界面的体内实时分布和迁移细节目前尚未清楚。我们前期已经成功开发了一种适合体内实时监测的短波红外荧光成像技术及其配套的纳米探针---水溶性硫化银量子点（sliver sulfide quantum dots, Ag2S QDs）。本项目拟通过荧光纳米探针Ag2S QDs体外标记BMSCs后，结合兔冈上肌腱损伤修补动物模型，利用短波红外荧光成像技术实时观测BMSCs在腱骨界面的体内动态过程，分析BMSCs的体内时空分布特征，探究BMSCs在此过程的迁移机制，为BMSCs作为促进腱骨愈合的治疗方案提供可靠的科学依据，也为深入研究腱骨愈合的提供新的思路和技术。

干细胞治疗为肩袖撕裂的修复提供了新思路。对移植细胞的命运进行示踪，如实时监测细胞在生物体内的迁移、生物分布等细胞行为，有利于综合评估干细胞治疗的有效性和安全性。本课题基于前期合成的 PbS 量子点，证实了近红外 IIa 区 PbS 量子点与间充质干细胞具有良好的生物相容性，利用近红外 IIa 区成像可视化了间充质干细胞在修复肩袖损伤时的命运，揭示了关节腔注射的间充质干细胞具有相似的迁移方向，但是细胞的迁移启动时间和停留时间与移植细胞数量相关，综合评估了干细胞治疗的有效性和安全性，有望为干细胞治疗的优化带来积极影响。其次，为了进一步提高成像的空间分辨率，本研究设计合成近红外 IIb 区 PbS/ZnS 量子点，描绘了小鼠多部位更详细的血管脉络结构，评估了成像探针的代谢特征和生物相容性，为活体血管动态研究提供有力工具。