A novel perfused muscle-on-chip platform to study muscle impairments in COPD

Le résumé fourni par la source

Skeletal muscle (SKM) is known to engage in inter-organ crosstalk. As SKM impairments in COPD arise together with lung pathology, it is plausible that SKM impairments arise after interactions with diseased lung tissue. However, platforms for studying the direct impact of lung cells on SKM are inadequate. We developed a novel muscle-on-chip (MoC) suitable for culturing and differentiation of SKM cells, which can be connected with lung-on-chips to study their interactions. Five candidate materials were assessed for biological compatibility with murine C2C12 myocytes cultured under static conditions. Brightfield microscopy revealed the best myotube formation on polystyrene (PS). Minimal required surface area for biochemical analyses was assessed, and chip dimensions and perfusion conditions were determined with computer simulations to mimic physiologically relevant shear stress. Based on these parameters, oxygen-permeable and -impermeable PS-based chips were designed to assess C2C12 differentiation under flow using brightfield imaging, myosin heavy chains (MyHC) immunofluorescent staining, and expression levels of myogenic and proliferation genes on day 0 vs day 6 of differentiation. Equal myotube formation and MyHC staining were observed in cells differentiated in both chips and mRNA expression of myogenic genes increased from day 0 to day 6 of differentiation, while the mRNA expression of proliferation markers decreased as expected. These data show that our novel MoC platforms are suitable for C2C12 myocyte culture and differentiation. This will allow connecting MoCs with lung-on-chips to study crosstalk in a COPD context, which can unveil new mechanisms and targets relevant for muscle impairments in COPD.

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