Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

Abstract

PURPOSE Rotator cuff injuries are associated with atrophy and fat infiltration into the muscle, commonly referred to as "fatty degeneration." As the poor function of chronically torn muscles may limit recovery after surgical repair, there is considerable interest in finding therapies to enhance muscle regeneration. Stromal vascular stem cells (SVFCs) can improve muscle regeneration in other chronic injury states, and our objective was to evaluate the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle fiber specific force production after chronic rotator cuff tear. METHODS Chronic supraspinatus tears were induced in adult immunodeficient rats, and repaired one month following tear. Rats received vehicle control, or injections of 3×105 or 3×106 human SVFCs into supraspinatus muscles. RESULTS Two weeks following repair, we detected donor human DNA and protein in SVFC treated muscles. There was a 40% reduction in fibrosis in the treated groups compared to controls (p=0.03 for 3×105, p=0.04 for 3×106), and no differences between groups for lipid content or force production were observed. CONCLUSIONS As there has been much interest in the use of stem cell-based therapies in musculoskeletal regenerative medicine, the reduction in fibrosis and trend towards an improvement in single fiber contractility suggest that SVFCs may be beneficial to enhance the treatment and recovery of patients with chronic rotator cuff tears.

Adipose‐derived stem cells delay muscle atrophy after peripheral nerve injury in the rodent model

“…This is consistent with previous investigations suggesting that ASC secretome is capable of reducing lipid content in rotator cuff injuries . This finding however, is not consistent amongst the literature where injections of human vascular and adipose‐derived stem cells isolated from human stromal vascular fraction did not display significant changes in lipid reduction …”

“…33 This finding however, is not consistent amongst the literature where injections of human vascular and adipose-derived stem cells isolated from human stromal vascular fraction did not display significant changes in lipid reduction. 34 Upon denervation, the local cellular environment of skeletal muscle becomes altered, where presence of inflammatory cells amongst the muscle fibers increases. 35 Dual-IF staining was performed to assess macrophage presence as macrophages are essential to muscle turnover in normal and degenerative states.…”

Cell therapy to improve regeneration of skeletal muscle injuries

“…In separate studies, Oh et al . and Gumucio et al . have reported the potential efficacy of adipose‐derived MSCs in repairing supraspinatus and subscapularis muscle tears and attenuating fibrosis in models of rotator cuff injury.…”

“…[127][128][129] BM-MSCs also improved muscle contractility by promoting new myofiber formation in a sphincterotomy injury model in rats, indicating their potential utility in treating incontinence. 130,131 In separate studies, Oh et al 132 and Gumucio et al 133 have reported the potential efficacy of adipose-derived MSCs in repairing supraspinatus and subscapularis muscle tears and attenuating fibrosis in models of rotator cuff injury. In injury models of volumetric muscle loss, improved muscle function (contractility) and structure (myofiber formation, reduction of scar tissue, increased blood vessel density) have been observed using MSCs from adipose tissue, 134,135 bone marrow, 136 cranial neural crest, 137 and tonsil.…”

Biologics and stem cell‐based therapies for rotator cuff repair

“…Finally, immediate repair after laceration also does not mimic the clinical scenario in which tendon tears are usually left untreated for weeks or months prior to repair. To model delayed repair, a few groups recently carried out supraspinatus tendon detachment followed by surgical repair 3–16 weeks later . Prolonged unloading resulted in tendon retraction, muscle atrophy, fatty infiltration, and fibrotic scarring.…”