Promoting Endogenous Cell Recruitment for Rotator Cuff Muscle Repair

促进内源性细胞募集以修复肩袖肌肉

基本信息

批准号：
10020758
负责人：
Johnna S Temenoff
金额：
$ 34.4万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10020758
关键词：
Aftercare Anti-Inflammatory Agents Atrophic Biocompatible Materials Bone Marrow Cell Communication Cell Separation Cell physiology Cells Chronic Clinical Complex Disease Elderly Engraftment Environment Fatty acid glycerol esters Fluorescence General Population Genes Glycosaminoglycans Goals Growth Factor Heparin Histology Human Hyaluronic Acid In Situ Inflammatory Injectable Injections Injury Ischemia Isometric Exercise Laboratories Lead Measures Mesenchymal Stem Cells Methodology Methods Mission Muscle Muscle Fibers Muscle function Muscle satellite cell Muscular Atrophy Muscular Dystrophies Myofibrils Natural regeneration Operative Surgical Procedures Outcome Outcome Measure Patient-Focused Outcomes Patients Production Proteins Public Health Rattus Regenerative Medicine Research Role Rotator Cuff Shoulder Site Stromal Cells TNF gene Techniques Tendon Injuries Tendon structure Testing Tissues United States National Institutes of Health Work base healing improved inflammatory milieu innovation macrophage muscle degeneration muscle regeneration particle prevent recruit repaired rotator cuff injury rotator cuff tear supraspinatus muscle therapeutic protein tissue regeneration tissue repair

项目摘要

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.

项目概要肩袖完全撕裂是一种使人衰弱的肌腱损伤，会导致肌腱萎缩和脂肪堆积。肩袖损伤治疗后相应肌肉的退化。与肩袖肌肉的质量直接相关，因此，逆转退行性变的方法。肌肉的变化将极大地改善肩袖撕裂患者的总体结果。与其他类型肌肉中发现的内源细胞募集和组织愈合之间的关键关系损伤，我们认为基质衍生因子 1α (SDF-1α) 和肿瘤坏死的共同传递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促进募集和植入的微环境抗炎巨噬细胞和间充质干细胞，从而促进旋转后的肌肉再生袖口肌腱撕裂。该应用的目的是确定骨局部植入之间的关系撕裂手术修复后骨髓源性细胞和肩袖肌肉的再生水平该目标将通过以下具体目标来实现： 1) 评估效果持续释放 SDF-1α 对大鼠冈上肌局部细胞募集和组织再生的影响肌腱复位后的肌肉和2)评估SDF-1α和TSG-6共同释放对局部的影响肌腱重新附着后大鼠冈上肌的细胞募集和组织再生。所提出的工作具有创新性，因为它采用了良好控制的可注射载体来实现持续释放并增强蛋白质疗法的效果以招募内源细胞为了扭转肩袖撕裂后的肌肉萎缩，这些研究的结果预计会得到。重要的积极影响，因为它们将带来更有效的再生医学疗法用于肩袖撕裂，并提供对哪些细胞参与的更深入的机制了解退化肌肉的愈合。