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

Abstract

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.

Rotator Cuff Repair and Overlay Augmentation by Direct Interlocking of a Nonwoven Polyethylene Terephthalate Patch Into the Tendon: Evaluation in an Ovine Model

“…In vivo biological response of the interlocked patch implant was characterized using a well-established ovine model of infraspinatus tendon tear. 16-19,21,27 Healing performance was based on macroscopic observations and histological analyses at 6 and 13 weeks after implantation. This study was approved by the local ethics committee and federal authorities for animal experiments (permission No.…”

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

“…In a sheep model, the administration of autologous MSCs in degenerated rotator cuff muscle was found to prevent muscle‐to‐fat conversion during the recovery phase following tendon repair. [ 80 ] This preservation of fat‐free mass was associated with extracellular reactions and the inhibition of adjuvant‐induced muscle fiber hypertrophy. One study discovered injection of allogenic MSC in fatty infiltrated supraspinatus muscle resulted in a significant increase in muscle mass compared to control group.…”

HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases

“…In recent years, stem cell therapy has been attempted as a cellular treatment for various skeletal muscle disorders. 12-14 These stem cells include, but are not limited to, MSCs, adipose-derived stem cells, hematopoietic stem cells, satellite cells, fibro-adipogenous progenitor cells, pericytes, and CD133 + stem cells. 15 Stem cell therapy involving these cells can promote skeletal muscle repair through various mechanisms.…”