Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Department of Orthopedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, 215008, China.
Biomaterials. 2021 Apr;271:120714. doi: 10.1016/j.biomaterials.2021.120714. Epub 2021 Feb 11.
Rotator cuff repair is a common surgery in sports medicine. During the surgery, torn tendon was re-fixed onto the bony surface. The majority of patients gain good results. However, re-tear occurs in some patients. The reason under this phenomenon is that the normal tendon-bone enthesis cannot be reconstructed. In order to strengthen the tendon-bone healing and promote enthesis regeneration, numerous manners are tested, among which stem cell related therapies are preferred. Stem cells, due to the ability of multi-lineage differentiation, are widely used in regenerative medicine. However, safety and ethics concerns limit its clinical use. Recent studies found that it is the secretome of stem cells that is biologically effective. On ground of this, we, in the current study, collected the conditioned medium of human bone marrow-derived stem cells (hBMSC-CM) and tested whether this acellular method could promote tendon-bone healing in a rat model of rotator cuff repair. By using histological, radiological, and biomechanical methods, we found that hBMSC-CM promoted tendon-bone healing of the rat rotator cuff. Then, we noticed that hBMSC-CM exerted an impact on macrophage polarization both in vivo and in vitro by inhibiting M1 phenotype and promoting M2 phenotype. Further, we proved that the benefit of hBMSC-CM on tendon-bone healing was related to its regulation on macrophage. Finally, we proved that, hBMSC-CM influenced macrophage polarization, which was, at least partially, related to Smad2/3 signaling pathway. Based on the experiments above, we confirmed the benefit of hBMSC-CM on tendon-bone healing, which relied on its immune-regulative property. Considering the accessibility and safety of acellular hBMSC-CM, we believe it is a promising candidate clinically for tendon-bone healing.
肩袖修复是运动医学中常见的手术。在手术过程中，撕裂的肌腱被重新固定在骨面上。大多数患者都能取得良好的效果。然而，一些患者会出现再次撕裂。这种现象的原因是正常的肌腱-骨结合无法重建。为了增强肌腱-骨愈合，促进结合处再生，人们尝试了许多方法，其中干细胞相关疗法较为受欢迎。由于具有多向分化的能力，干细胞广泛应用于再生医学。然而，安全性和伦理学问题限制了其临床应用。最近的研究发现，干细胞的分泌组具有生物学效应。基于这一点，我们在当前的研究中收集了人骨髓间充质干细胞（hBMSC-CM）的条件培养基，并测试了这种无细胞方法是否能促进大鼠肩袖修复模型中的肌腱-骨愈合。通过组织学、影像学和生物力学方法，我们发现 hBMSC-CM 能促进大鼠肩袖的肌腱-骨愈合。然后，我们注意到 hBMSC-CM 通过抑制 M1 表型和促进 M2 表型，在体内和体外都对巨噬细胞极化产生影响。此外，我们证明了 hBMSC-CM 对肌腱-骨愈合的益处与其对巨噬细胞的调节有关。最后，我们证明了 hBMSC-CM 影响巨噬细胞极化，至少部分与 Smad2/3 信号通路有关。基于上述实验，我们证实了 hBMSC-CM 对肌腱-骨愈合的益处，这依赖于其免疫调节特性。考虑到无细胞 hBMSC-CM 的可及性和安全性，我们相信它在临床上是一种很有前途的肌腱-骨愈合候选物。
