Sarcopenic muscle extracellular matrix dictates muscle adaptations in a 3D-engineered muscle model of COPD

Introduction: We investigated whether exercie-induced extracellular matrix (ECM) protein expression from sarcopenic COPD can replicate muscle wasting and loss of muscle strength in a 3D-engineered muscle.

Methods: Exercise-induced changes in ECM composition in sarcopenic COPD muscle (FFMI; 15.6 Kg.cm2, n=10) and healthy people (FFMI; 19.4 Kg.cm2, n=18) were replicated in a xeno-free human 3D-engineered muscle tissue organoid. Human myoblasts (Lonza) embedded in specific ECM composition from COPD sarcopenic and healthy people were used to construct a 3D-muscle model. Muscle fibre width, and protein expression was analysed using immune fluorescence (IF) images. Gene expression was quantified using RT-PCR.

Results: Compared to healthy, treatment with increasing amount of ECM proteins from sarcopenic COPD induced muscle fibre wasting and failure in myoblast cell attachment and differentiation (Figure 1). Sarcopenic COPD compared to healthy ECM composition produced myofibers with shorter length and smaller width evidenced by IF analyses of anti-sarcomeric α-actinin and anti-desmin staining. Myogenic and growth factors were also affected by ECM compositionn from sarcopenic COPD.

Conclusion: Compared to healthy, muscle from sarcopenic COPD presents particular ECM composition that does not favour exercise-induced muscle growth.