Engineered skeletal muscles for disease modeling and drug discovery

Can we mimic skeletal muscles for novel drug discovery?

“…Currently, the use of composite fibrin-Matrigel hydrogels yields engineered skeletal muscle tissues with the highest force generation capacity. These tissues support both the formation of mature aligned muscle fibers (Figure 1(b-c)) and maintenance of a functional satellitelike cell pool, thereby allowing studies of muscle development, function, and regeneration in a single system [1].…”

“…The SCs can be activated and differentiate to repair small muscle injuries and are the only robust source of myogenic progenitor cells (MPCs) in skeletal muscle. Human skeletal muscle has been modeled in vitro using primary, immortalized, and human-induced pluripotent stem cell (hiPSC)-derived MPCs [1]. Primary MPCs are the current gold standard cell source but have limited proliferative ability, lose their myogenic and engraftment potential with serial passaging, and may be hard to obtain due to ethical reasons.…”

“…This includes the ability to expand large numbers of aged SCs and/or identify conditions to faithfully age primary SCs or iMPCs for accurate modeling of sarcopenia. Optimized regimes of biophysical stimulation and combinatorial uses of growth factors, small molecules, and metabolic fuel sources will be needed to accelerate engineered muscle maturation in weeks rather than years [1,6]. Biomimetic incorporation of other muscle-resident cells such as fibroblasts, motor neurons [10], and immune [11] and vascular [12,13] cells will allow more accurate modeling of native muscle composition, function, regeneration, and complex disease phenotypes.…”

“…Skeletal muscle is a highly regenerative tissue that produces contractile forces required for respiration and locomotion and aids regulation of whole-body energy homeostasis via postprandial glucose uptake [1]. Impairment in skeletal muscle function and/or regenerative ability can occur due to cancer, aging, trauma, and genetic muscular diseases, such as Duchenne Muscular Dystrophy (DMD).…”

Pre-Clinical Cell Therapeutic Approaches for Repair of Volumetric Muscle Loss

“…An improved understanding of the molecular and cellular interactions of muscle regeneration will facilitate the engineering of an optimal microenvironment to guide therapeutic cells toward restoring muscle function after VML. Exploiting emerging technologies, such as on-chip disease models and Slide-Seq, will help in probing the role of different cells present at VML injury sites at the molecular and genomic levels [54,55]. Understanding the complex multicellular and ECM interactions of the inflammatory microenvironment of VML could open new windows for selecting an optimized combination of myogenic and non-myogenic cells in an engineered microenvironment niche in order to induce de novo muscle regeneration.…”