3D in vitro Models of Pathological Skeletal Muscle: Which Cells and Scaffolds to Elect?

Abstract

Skeletal muscle is a fundamental tissue of the human body with great plasticity and adaptation to diseases and injuries. Recreating this tissue in vitro helps not only to deepen its functionality, but also to simulate pathophysiological processes. In this review we discuss the generation of human skeletal muscle three-dimensional (3D) models obtained through tissue engineering approaches. First, we present an overview of the most severe myopathies and the two key players involved: the variety of cells composing skeletal muscle tissue and the different components of its extracellular matrix. Then, we discuss the peculiar characteristics among diverse in vitro models with a specific focus on cell sources, scaffold composition and formulations, and fabrication techniques. To conclude, we highlight the efficacy of 3D models in mimicking patient-specific myopathies, deepening muscle disease mechanisms or investigating possible therapeutic effects.

Leveraging Biomaterial Platforms to Study Aging-Related Neural and Muscular Degeneration

“…However, microscopic observations of muscle tissue have shown that this classification may be relatively arbitrary and that the endomysium and perimysium form two continuous 3D networks [211,213]. Furthermore, according to some classification schemes, the basal lamina is considered to be a distinct structure from the endomysium; however, they are in close contact, and in some instances, the basal lamina has been described as a specialized form of endomysium [214,215]. Generally, the major component of muscle ECM is collagen, accounting for up to 10% of its dry weight [200,211].…”

“…The epimysium is formed of collagen type I, collagen type III, and fibronectin; the perimysium contains fibronectin, proteoglycans, and collagens I, III, V, and VI; and the endomysium is composed of laminin, fibronectin, and collagens I, III, and V [218][219][220][221]. Collagen IV, the collagenous component of basement membranes, has also been isolated from the endomysium, where it links with laminin to form a complex involved in force transduction [214,218]. Some studies suggest that collagen type I is the main component of intramuscular ECM and that it is abundant in the perimysium and epimysium, while collagen type III is evenly distributed between the endomysium and the epimysium [214,218,222].…”

“…Collagen IV, the collagenous component of basement membranes, has also been isolated from the endomysium, where it links with laminin to form a complex involved in force transduction [214,218]. Some studies suggest that collagen type I is the main component of intramuscular ECM and that it is abundant in the perimysium and epimysium, while collagen type III is evenly distributed between the endomysium and the epimysium [214,218,222]. However, further investigation with standardized models is required to reach a consensus on the muscle matrix composition and to determine whether collagen-type ratios vary between muscles with different functions [211].…”

“…The generation of skeletal muscle tissue in vitro requires the integration of multiple cell types and the recreation of the extracellular environment and tissue architecture. The latter is a particular challenge in muscle tissue engineering due to the complexity of its hierarchical organization [214]. While the hallmark cell types in skeletal muscle tissue are myofibers and muscle stem cells, other crucial cell populations that can be found in muscle include fibroblasts and fibro-adipogenic progenitors, pericytes, endothelial cells, neural cells, and immune cells.…”

Human Adipose-Derived Stromal Cells Delivered on Decellularized Muscle Improve Muscle Regeneration and Regulate RAGE and P38 MAPK

“…In VML injuries, the MuSC pool is depleted through the loss of muscle volume, infringing on muscle’s inherent regenerative capacity [ 1 , 2 ]. In addition, extracellular matrix (ECM) accounts for ~10% of the skeletal muscle mass and coats muscle fibers and MuSCs [ 3 ]. Loss of the ECM eliminates a key element in muscle regeneration.…”