Transplant of Autologous Mesenchymal Stem Cells Halts Fatty Atrophy of Detached Rotator Cuff Muscle After Tendon Repair: Molecular, Microscopic, and Macroscopic Results From an Ovine Model

Background: The injection of mesenchymal stem cells (MSCs) mitigates fat accumulation in released rotator cuff muscle after tendon repair in rodents. Purpose: To investigate whether the injection of autologous MSCs halts muscle-to-fat conversion after tendon repair in a large animal model for rotator cuff tendon release via regional effects on extracellular fat tissue and muscle fiber regeneration. Study Design: Controlled laboratory study. Methods: Infraspinatus (ISP) muscles of the right shoulder of Swiss Alpine sheep (n = 14) were released by osteotomy and reattached 16 weeks later without (group T; n = 6) or with (group T-MSC; n = 8) electropulse-assisted injection of 0.9 Mio fluorescently labeled MSCs as microtissues with media in demarcated regions; animals were allowed 6 weeks of recovery. ISP volume and composition were documented with computed tomography and magnetic resonance imaging. Area percentages of muscle fiber types, fat, extracellular ground substance, and fluorescence-positive tissue; mean cross-sectional area (MCSA) of muscle fibers; and expression of myogenic (myogenin), regeneration (tenascin-C), and adipogenic markers (peroxisome proliferator-activated receptor gamma [PPARG2]) were quantified in injected and noninjected regions after recovery. Results: At 16 weeks after tendon release, the ISP volume was reduced and the fat fraction of ISP muscle was increased in group T (137 vs 185 mL; 49% vs 7%) and group T-MSC (130 vs 166 mL; 53% vs 10%). In group T-MSC versus group T, changes during recovery after tendon reattachment were abrogated for fat-free mass (–5% vs –29%, respectively; P = .018) and fat fraction (+1% vs +24%, respectively; P = .009%). The area percentage of fat was lower (9% vs 20%; P = .018) and the percentage of the extracellular ground substance was higher (26% vs 20%; P = .007) in the noninjected ISP region for group T-MSC versus group T, respectively. Regionally, MCS injection increased tenascin-C levels (+59%) and the water fraction, maintaining the reduced PPARG2 levels but not the 29% increased fiber MCSA, with media injection. Conclusion: In a sheep model, injection of autologous MSCs in degenerated rotator cuff muscle halted muscle-to-fat conversion during recovery from tendon repair by preserving fat-free mass in association with extracellular reactions and stopping adjuvant-induced muscle fiber hypertrophy. Clinical Relevance: A relatively small dose of MSCs is therapeutically effective to halt fatty atrophy in a large animal model.

CT-based volumetric assessment of rotator cuff muscle in shoulder arthroplasty preoperative planning

Aims The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561.

Vitamin D level in the rotator cuff muscle and serum correlates with postoperative muscle performance at 1 year after rotator cuff repair

Objectives: Previously, we reported that tissue vitamin D (tVD) in the rotator cuff muscle had strong correlation with pre-operative serum vitamin D (sVD). Furthermore, tVD reflected more on the preoperative muscle power. This study was a follow-up study to evaluate correlations of tVD, vitamin D receptor (VDR), and postoperative sVD with rotator cuff muscle performance, fatty degeneration, healing failure, and functional outcomes at 1 year after rotator cuff repair (RCR). Methods: Between March and October in 2017, 36 patients who underwent RCR were prospectively enrolled and 26 patients were followed at 1 year postoperatively and analyzed. tVD was assessed using liquid chromatography, and the VDR was measured by western blotting. sVD was checked preoperatively, 6 months, and 1 year post-operatively. At 1 year after surgery, isokinetic muscle performance test (IMPT), ASES score and Constant score were evaluated, and MRI was used to analyze fatty degeneration and the healing failure. Results: The mean level of sVD at 1 year post-operatively was 20.5 ± 9.2 ng/ml. Only six patients had normal level of sVD (> 20 ng/ml, 23.1%), while 19 patients had insufficiency (10 - 20 ng/ml, 73.0%), and one patient had defi-ciency (< 10 ng/ml, 3.8%). Lower sVD at pre-operatively had lower sVD at 6 months and 1 year post-operatively (all p < 0.05). Higher pre-operative and 1 year post-operative sVD had less deficiency of IMPT in abduction (pre-operative, post-operative; CC; Abduction, -0.324, -0.395, p = 0.047, 0.041, respectively) How-ever, no correlation was found in deficiency of IMPT in ER, IR (pre-operative, post-operative; CC; ER, IR; 0.025, -0.042; p = 0.926, 0.874, respectively; post-operative; CC; ER, IR; -0.250, -0.157; p = 0.333, 0.548, re-spectively). Although, there was no correlation was found between torque of muscle power at 1 year post-operatively with pre- and post-operative sVD (all p > 0.05), higher tVD had higher torque of abduction (CC: 0.440, p = 0.043), and showed tendency of higher torque of external rotation (ER) (CC: 0.335, p = 0.077). There was no correlation of tVD and sVD with functional outcomes, fatty degeneration and re-tear rate (all p > 0.05). VDR showed no correlation with any variables (all p > 0.05). Conclusions: tVD and sVD showed positive correlation with rotator cuff muscle performance at 1 year after RCR. Regarding lower sVD at pre-operatively had lower sVD at 1 year post-operatively, and considering lower sVD had higher deficiency of muscle power, supplementation of vitamin D to these patients with low sVD would enhance rota-tor cuff muscle performance postoperatively.