Endogenous stem cells promote regeneration of muscle in rotator cuff repair

肩袖撕裂是最常见的上肢损伤，超过200万美国人 每年寻求医疗救治。随着退伍军人年龄的增加，RC的眼泪是 成为退伍军人管理局患者的一个重要健康问题。撕裂后肌肉继发退化， 包括萎缩和脂肪渗透(FI)是直接决定临床的关键因素。 有这种损伤的患者的结局。肌肉纤维/成脂祖细胞(FAP)具有 被发现是肌腱大规模撕裂后RC肌肉中脂肪的主要细胞来源。我们最近 发现这些细胞代表了一个异质细胞群体，既能再生又能 肌肉损伤的病理反应。重要的是，FAP可以分化成米色的脂肪组织。 (BAT)在慢性损伤中可能具有促进肌肉恢复和再生作用的表型 各州。然而，目前还没有研究评估影响FAP命运的因素 人体袖口撕裂，也不知道FAP在临床场景中的再生能力，如旋转器 袖口修补。临床上，患者的年龄和肩袖撕裂的大小都被发现 与较差的肌肉质量和较差的患者预后相关的独立因素。然而， 患者与肩袖撕裂大小的相互作用及其对肌肉干细胞的影响 增殖、分化和再生能力目前尚不清楚。要解决这个问题 问题，我们将进行第一个评估FAP表型特性的大规模临床研究 肩袖撕裂的患者。扩展我们前景看好的小鼠研究，表明FAP具有 为了刺激肌肉再生，我们将进行一系列严格的研究，以确定 人类FAP在这一临床相关场景中的再生能力证实了我们的假设 FAP促进健康肌肉再生的能力取决于撕裂的大小和 患者的年龄因FAP基因表达的变化。在这项研究结束时，我们将理解 临床上重要的因素(年龄、泪液大小)如何影响皮肤退行性变和再生潜能 人类FAPs，这应该提供关于这些内源性干细胞如何 利用有针对性的治疗策略在近期改善精确指导的患者结果 未来。

Rotator cuff (RC) tears are the most common upper extremity injury, with over two million Americans seeking medical attention annually. With the increased age of our veterans' population, RC tears are becoming a vital health issue for the VA patients. Secondary muscle degradation following tears, including atrophy and fatty infiltration (FI) are critical factors that directly determine the clinical outcome of patients with this injury. Muscle residential fibro/adipogenic progenitor (FAP) cells have been found to be the major cellular source of fat in RC muscle after massive tendon tears. We recently discovered that these cells represent a heterogeneous cell population capable of both regenerative and pathologic responses to muscle injury. Importantly, FAPs can differentiate into a beige adipose tissue (BAT) phenotype that may have a role in promoting muscle recovery and regeneration in chronic injury states. However, at this time, no studies have evaluated factors that influence the fate of FAPs in human cuff tears, nor what FAP regenerative capabilities could be in clinical scenarios such as rotator cuff repair. Clinically, both patient age and size of the rotator cuff tear have been found to be independent factors that associate with poorer muscle quality and worse patient outcomes. However, the interplay between patient and rotator cuff tear size and their influence on muscle stem cell proliferation, differentiation, and regenerative capabilities is not known at this time. To address this problem, we will perform the first large-scale clinical study evaluating FAP phenotypic properties in patients with rotator cuff tears. Expanding on our promising mouse studies that show FAPs are capable of stimulating muscle regeneration, we will perform a rigorous set of studies that will determine the regenerative capabilities of human FAPs in this clinically relevant scenario to confirm our hypothesis that the ability of FAPs to promote healthy muscle regeneration is dependent on the size of the tear and age of the patient due to changes in FAP gene expression. By the end of this study, we will understand how clinically important factors (age, tear size) affect the degeneration and regeneration potential of human FAPs, which should provide critical information on how these endogenous stem cells can be leveraged to improve precision guided patient outcomes with targeted therapeutic strategies in the near future.