Improving muscle quality and enhancing shoulder function following rotator cuff injury through blood flow restriction therapy

Rotator cuff tearing, a pervasive age-related shoulder injury, imposes a substantial burden on millions of patients in the United States, particularly within our aging Veteran population. Up to 20% of individuals over 50 exhibit symptomatic rotator cuff tears, and nearly half of those aged 70 or older are grappling with this condition. Shoulder pain and dysfunction emerge as the major symptoms for patients with rotator cuff tears. While non-surgical treatments prove effective for smaller tears, the management of larger or massive rotator cuff tears demands surgical repair. Poor muscle quality stands out as a critical contributor to the failure of rotator cuff tendon repairs, emphasizing the pivotal role of enhancing muscle quality for advancing clinical outcomes in patients with rotator cuff repairs. In the past decade, our laboratory has been at the forefront of unraveling the complexities of rotator cuff muscle degeneration and regeneration. Our groundbreaking studies have elucidated the role of muscle stem cells, specifically fibro/adipogenic progenitors (FAPs), in this context. Notably, our findings in both mice and humans have demonstrated the transformative potential of inducing FAP brown/beige fat (BAT) differentiation and horizontal mitochondria transfer toward myocytes. These mechanisms effectively reduce muscle degeneration and promote shoulder function post-rotator cuff tears. Though the detailed mechanism remains unknown, blood flow restriction (BFR) therapy, a method that temporarily limits blood flow in limbs, emerges as a promising intervention in reducing muscle atrophy and musculoskeletal pain. Our recent endeavors to unlock this mystery have uncovered the potential benefits of BFR in stimulating FAP BAT differentiation and horizontal mitochondria transfer during muscle regeneration. Adding to our arsenal of innovation, we've developed a low-cost tool employing machine learning techniques to quantitatively assess shoulder function. This tool, analyzing hand-over-hand string-pulling motions, provides a reliable means of evaluating shoulder health in both animal models and human subjects with rotator cuff tears. Additionally, our novel machine-learning approach utilizes the Blackbox® system to measure mechanical pain in mice following rotator cuff tears, offering a nuanced understanding of pain dynamics. Looking ahead, our proposed study aims to push the boundaries of innovation further. In this proposed study, we aim to define the role of BFR in a preclinical rotator cuff tears and repair model to evaluate the effectiveness of BFR in stimulating FAP BAT differentiation and mitochondria transfer, reducing muscle atrophy and degeneration, enhancing shoulder function, and alleviating pain. This groundbreaking research aligns with our vision of translating innovative findings from the laboratory to future clinical trials, promising impactful outcomes for patients with rotator cuff tears, particularly within the aging veteran population. Project Number: 1I01RX005293-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Xuhui Liu | Institution: VETERANS AFFAIRS MED CTR SAN FRANCISCO, SAN FRANCISCO, CA | Activity Code: I01 | Study Section: Musculoskeletal Health & Function[RRD2] View on NIH RePORTER: https://reporter.nih.gov/project-details/11102226