Utilizing beige fat to improve muscle function after rotator cuff repair

利用米色脂肪改善肩袖修复后的肌肉功能

• 批准号: 10645657
• 负责人: Brian Feeley
• 金额: $ 11.55万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10645657
• 关键词: Adipocytes; Adipose tissue; Affect; Age-Years; American; Animal Model; Animals; Anterior; Atrophic; Cell Differentiation process; Cell physiology; Cells; Clinical; Coculture Techniques; Data; Development; Diabetes Mellitus; Economic Burden; FRAP1 gene; Failure; Fatty acid glycerol esters; Follistatin; Gene Expression; Grant; Growth; Health Care Costs; Human; In Vitro; Infiltration; Injury; Insulin-Like Growth Factor I; Knowledge; Link; Metabolic; Molecular; Mus; Muscle; Muscle function; Muscular Atrophy; Myopathy; Operative Surgical Procedures; Outcome; Outcome Study; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Pharmacological Treatment; Pharmacology; Phenotype; Population; Process; Production; Productivity; Proliferating; Quality of life; Recovery; Role; Rotator Cuff; Shoulder Pain; Source; Thermogenesis; Transgenic Mice; Translating; Upper Extremity; Wages; Work; adipokines; age group; aged; cell type; clinically significant; clinically translatable; disability; experimental study; gain of function; gait examination; human old age (65+); human tissue; improved; injured; injury and repair; interest; limb injury; loss of function; medical attention; mouse model; muscle degeneration; muscle regeneration; novel; overexpression; physically handicapped; progenitor; repair model; repaired; rotator cuff injury; rotator cuff tear; satellite cell; shoulder injury; stem cell population; stem cells; success; supraspinatus muscle; surgery outcome; therapeutic target; treatment strategy

123 PROJECT DESCRIPTION 45 Rotator cuff (RC) tears are an extremely common cause of shoulder pain and disability. Up to 50% of patients greater than the age of 65 years of age have evidence 6789 of a RC tear. In addition, patients with small asymptomatic cuff tears tend to progress to larger, symptomatic tears. The outcomes of surgical repair of small RC tears are good, but there has been limited success in the surgical treatment of massive RC tears. 11 01 Massive RC tears have been linked with fatty infiltration of the rotator cuff muscles. Patients with large RC tears who develop fatty infiltration have poorer clinical outcomes 11 23 and higher rates of failure after attempted repair. We have previously found that a newly discovered stem cell population-fibro/adipocyte progenitor (FAP) cells-is critical in the 11 45 development of fatty infiltration after RC injury. Further, these cells share similar expression patterns with the beige adipocyte lineage, a distinct cell population that has 11 67 unique thermogenic and metabolic capabilities that could improve muscle function. 11 89 The study will leverage our well-studied animal model and a novel repair model to evaluate the mechanism by which FAP cells can improve muscle function through 22 01 differentiation into a beige fat phenotype in mouse and human tissue. Understanding the relationship between FAP cells and beige adipocytes and utilizing these cells in endogenous and exogenous treatment strategies could help improve muscle quality in RC repair as well as other muscle injury states.

123 项目描述 45 肩袖（RC）眼泪是肩痛和 残疾。大于65岁的患者中，多达50％的患者有证据 6789 rc撕裂。此外，小无症状袖口泪的患者往往会发展 更大的有症状的眼泪。小RC眼泪的手术修复的结果很好， 但是在大规模RC撕裂的手术治疗方面取得了有限的成功。 11 01 大量的RC泪液与肩袖肌肉的脂肪浸润有关。 大量RC泪水浸润的患者的临床结局较差 11 23 尝试修复后的失败率更高。我们以前已经发现一个新的 发现干细胞群/脂肪细胞祖细胞（FAP）细胞在 11 45 RC损伤后脂肪浸润的发展。此外，这些细胞共享相似 具有米色脂肪细胞谱系的表达模式，这是一种不同的细胞群 11 67 可以改善肌肉功能的独特热和代谢能力。 11 89 该研究将利用我们研究精心的动物模型和新颖的维修模型来 评估FAP细胞可以通过 22 01 分化为小鼠和人体组织中的米色脂肪表型。了解 FAP细胞与米色脂肪细胞之间的关系，并利用这些细胞 内源和外源治疗策略可以帮助提高肌肉质量 RC修复以及其他肌肉损伤状态。