A Novel Minimally Invasive Surgically Induced Skeletal Muscle Injury Model in Sheep.
Laura VidalIngrid VilaVanesa VenegasAnabel SacristánPaola Contreras-MuñozMaria Lopez-GarzonCarles GinéGil RodasMario MarottaPublished in: International journal of molecular sciences (2024)
Sports-related muscle injuries account for 10-55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences ( p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.
Keyphrases
- skeletal muscle
- endothelial cells
- insulin resistance
- magnetic resonance imaging
- ultrasound guided
- minimally invasive
- contrast enhanced
- computed tomography
- ejection fraction
- end stage renal disease
- metabolic syndrome
- induced pluripotent stem cells
- high glucose
- machine learning
- pluripotent stem cells
- peritoneal dialysis
- robot assisted
- prognostic factors
- patient reported outcomes
- wound healing
- sensitive detection
- dual energy
- loop mediated isothermal amplification
- gestational age