载氧化铁PLGA纳米粒多模态示踪肌腱干细胞促进肩袖损伤修复的基础研究

Rotator cuff injury is the main cause of shoulder pain and disability. While, it is still very difficult to repair the injured rotator cuff. Tendon stem cells(TSCs) show a great potency and application future in tendon regeneration and function rehabilitation, because of their regenerative capabilities and multidifferentiation potentials. However, there is not a method that is capable of real-time, visuable monitoring of TSCs, which makes it difficult to analyze the biological behaviors of TSCs，and then will prevents the development and the clinical application of TSCs for rotator cuff repair. This study combines the advantages of ultrasound, photoacoustic imaging, and MRI technology basis and our preliminary studies to built a multifunctional cell tracers loaded with PLGA nanoparticles, to achieve in vivo, real-time, non-invasive, and quantificational monitoring TSCs in vivo, to explore TSCs’ survival, retention, distribution, migration when repairing rotator cuff, and to explore the mechanism of which TSCs stimulate tendon healin. Meanwhile, this study will achieve the visuable repair of rotator cuff, and then provide scientific evidence for clinical translational medicine directly and objectivelly.

肩袖损伤是顽固性肩部疼痛和功能障碍的主要病因，肩袖损伤的修复目前仍然是一个难题。肌腱干细胞（tendon stem cells, TSCs）具有良好的克隆增殖能力及多向分化潜能，在肌腱的再生和功能重建方面具有巨大的潜能和应用前景。然而目前仍没有一种方法能实时、可视化监控TSCs，不利于揭示TSCs移植后的存活、滞留、分化、迁移等规律，阻碍了TSCs促进肌腱损伤修复的研究进展和临床应用。本项目拟结合超声、光声和核磁共振成像技术的优势及前期构建的一种可用于多模态显像的Fe3O4/PLGA纳米粒，研制出一种多功能干细胞示踪剂，用于实现对TSCs的活体、实时、无创、定量的多模态监测，揭示肩袖损伤修复过程中TSCs的生物学行为特征，阐明TSCs促进肌腱损伤修复的作用机制，为下一步可视化诱导TSCs定向分化奠定基础，为临床转化医学研究提供科学依据。

肩袖损伤是顽固性肩部疼痛和功能障碍的主要病因,肩袖损伤的修复目前仍然是一个难题。肌腱干细胞(tendon stem cells,TSCs)具有良好的克隆增殖能力及多向分化潜能,在肌腱的再生和功能重建方面具有巨大的潜能和应用前景。然而目前仍没有一种方法能实时、可视化监控TSCs,不利于揭示TSCs移植后的存活、滞留、分化、迁移等规律,阻碍了TSCs促进肌腱损伤修复的研究进展和临床应用。本项目应用载氧化铁聚乙乳酸羟基乙酸微粒（PLGA/IOMPs）体外标记肌腱干细胞（TSCs），并通过光声（PA）/核磁共振（MR）成像双模态示踪体内移植后标记TSCs，探讨PA/MR双模态体内示踪TSCs的可行性和TSCs促进大鼠肩袖损伤修复的疗效。本项目发现PLGA/IOMPs具有体内、外长期标记TSCs的可行性，能被MRI和PA成像显示，且标记的TSCs能有效促进大鼠肩袖损伤的修复，提高肌腱生物力学性能。随着纳米医学和再生医学的结合，基于纳米材料多模态成像的细胞示踪技术将会被广泛地应用于探索干细胞治疗各种疾病如中风、帕金森病、心肌梗死等的研究中，进一步推动干细胞治疗的临床转化。