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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：
10254285
负责人：
Johnna S Temenoff
金额：
$ 33.35万
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 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10254285
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 stem cell engraftment 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.

项目总结