基于MRI UTE成像从单细胞水平研究骨髓间充质干细胞促进肩袖术后腱骨愈合的机制

肩袖撕裂的发生率很高，在中老年人中尤为常见。目前症状性撕裂的治疗以修复手术为主。肩袖是一种无法再生组织、术后腱骨连接区(TBI)只能形成瘢痕组织，再撕率高达94%。骨髓来源间充质干细胞（BMSCs）能够向组织中各个谱系分化，在促进TBI再生愈合中能发挥重要作用；但其定向分化机制尚不清晰，阻碍了干细胞疗法向临床应用的转化。本项目成功建立兔肩袖损伤修复模型，通过纵向研究证实MRI UTE能对术后肩袖TBI愈合过程进行无创定量评估，并证实BMSCs在肩袖修补术后TBI愈合中发挥促进作用。为了进一步揭示愈合过程中BMSCs定向分化的机制，本实验将采用单细胞测序技术解析该过程不同阶段的基因表达差异及细胞动态构成，并将基因表达量与定量UTE指标进行相关性分析筛选出愈合情况相关的预测基因。研究所获结果将为解码TBI再生的BMSCs定向分化体系奠定基础，有助于促进干细胞应用于肩袖愈合向临床转化。

Rotator cuff tears have a high incidence, especially in middle-aged and elderly people. At present, the treatment of symptomatic tears is mainly repair surgery. However, only scar tissue can be formed in the tendon-bone interface (TBI) after rotator cuff surgery since it is a kind of non-regeneratable tissue, and the re-tear rate was reported to be up to 94%. Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into various lineages, enable it playing a role in promoting the regeneration and healing of TBI; however, the directed differentiation mechanism during this process is not clear, which hinders the translation of stem cell therapy to clinical applications. In our previous studies, a rabbit rotator cuff repair model was successfully established. Furthermore, longitudinal studies have confirmed that MRI UTE can perform as a non-invasive quantitative assessment of the postoperative TBI healing process and confirmed that BMSCs play a role in promoting TBI healing after rotator cuff repair. In order to further reveal the directed differentiation mechanism of BMSCs, we will use single cell sequencing technology to analyze the differences in gene expression and cell dynamics at different stages of the process, and analyze the correlation between gene expression and quantitative UTE indicators to screen out healing-related predictive genes. The results of the research will lay the foundation for decoding the targeted differentiation system of BMSCs for TBI regeneration and help promote the clinical translation of stem cells into the treatment of rotator cuff TBI healing.