Promoting Endogenous Cell Recruitment for Rotator Cuff Muscle Repair

项目摘要 完全性肩袖撕裂是一种使人衰弱的肌腱损伤，导致肌肉萎缩和脂肪堆积。 相应肌肉的退化。肩袖损伤治疗后的临床结局 与肩袖肌肉的质量直接相关。因此，逆转退化的方法 肌肉的变化将大大改善肩袖撕裂患者的总体结局。由于 在其他类型的肌肉中发现的内源性细胞募集和组织愈合之间的关键关系 我们认为，基质衍生因子1α（SDF-1α）和肿瘤坏死因子（TNF-α） 来自为每个分子定制的基于糖胺聚糖的载体的因子刺激基因-6（TSG-6）将 在肩袖肌肉中创造一个微环境，以鼓励招募和植入 抗炎巨噬细胞和骨髓间充质干细胞，因此促进肌肉再生后旋转 肩袖肌腱撕裂。 本申请的目的是确定骨的局部植入之间的关系， 肩袖撕裂修复术后骨髓源性细胞与肩袖肌再生水平的关系 肌腱将通过以下具体目标实现这一目标：1）评估 持续释放SDF-1α对大鼠冈上肌局部细胞募集和组织再生的影响 2）评估SDF-1α和TSG-6的共同释放对局部肌松的影响， 肌腱再附着后冈上肌细胞募集和组织再生。 拟议的工作是创新的，因为它采用了一个控制良好的，可注射的载体，以实现 持续释放以及增强蛋白质治疗剂募集内源性细胞的作用， 以逆转肩袖撕裂后的肌肉萎缩。这些研究的结果预计将有 一个重要的积极影响，因为它们将导致更有效的再生医学疗法 对于肩袖撕裂，以及提供更大的机械理解，哪些细胞参与 退化肌肉的愈合。

PROJECT SUMMARY Complete rotator cuff tears are a debilitating tendon injury that result in the atrophy and fatty degeneration of the corresponding muscle. Clinical outcomes following treatment of rotator cuff injuries are directly related to the quality of the rotator cuff muscle. Therefore, methods to reverse degenerative changes in the muscle would greatly improve overall outcomes for patients with rotator cuff tears. Due to the key relation between endogenous cell recruitment and tissue healing found in other types of muscle injury, we believe that the co-delivery of both stromal derived factor 1α (SDF-1α) and tumor necrosis factor-stimulated gene-6 (TSG-6) from glycosaminoglycan-based carriers tailored for each molecule will create a microenvironment in the rotator cuff muscle that will encourage recruitment and engraftment of anti-inflammatory macrophages and MSCs and therefore promote muscle regeneration after rotator cuff tendon tears. The objective of this application is to determine the relationship between local engraftment of bone marrow-derived cells and the level of regeneration of rotator cuff muscle after surgical repair of the torn tendon. This objective will be approached through the following specific aims: 1) Evaluate the effects of sustained release of SDF-1α on local cell recruitment and tissue regeneration in the rat supraspinatus muscle after tendon reattachment and 2)Evaluate the effects of co-release of SDF-1α and TSG-6 on local cell recruitment and tissue regeneration in the rat supraspinatus muscle after tendon reattachment. The proposed work is innovative because it employs a well-controlled, injectable carrier to achieve sustained release as well as enhance the effects of protein therapeutics to recruit endogenous cells in order to reverse muscle atrophy after rotator cuff tears. Results from these studies are expected to have an important positive impact because they will lead to more efficacious regenerative medicine therapies for rotator cuff tears, as well as provide greater mechanistic understanding of which cells participate in healing of degenerate muscle.