Bioengineered 3D Skeletal Muscle Model Reveals Complement 4b as a Cell‐Autonomous Mechanism of Impaired Regeneration with Aging

• DOI: 10.1002/adma.202207443
• Publication Date: 2023-01-18T04:01:41Z
• Authors: Kai Wang; Stephen H. Smith; Hirotaka Iijima; Zachary R. Hettinger; Adarsh Mallepally; Sanjeev G. Shroff; Fabrisia Ambrosio
• Keywords: Mammals; Aging; Muscle Fibers, Skeletal; Complement C4b; Animals; Muscle, Skeletal; Muscle Contraction

A mechanistic understanding of cell-autonomous skeletal muscle changes after injury can lead to novel interventions improve functional recovery in an aged population. However, major knowledge gaps persist owing limitations traditional biological aging models. 2D cell culture represents artificial environment, while mammalian models are contaminated by influences from non-muscle cells and other organs. Here, a 3D system is created overcome the these platforms. It shown that old constructs (OMC) manifest sarcopenic phenotype, as evidenced hypotrophic myotubes, reduced contractile function, decreased regenerative capacity compared young constructs. OMC also phenocopy responses two interventions, pharmacological biological. Interrogation cell-specific mechanisms contribute impaired regeneration over time further reveals aging-induced increase complement component 4b (C4b) delays progenitor amplification impairs recovery. administration factor I, C4b inactivator, improves vitro vivo, indicating inhibition may be approach enhance repair. Collectively, model herein exhibits capabilities study during aging, regeneration, intervention.