Investigating monocytes - skeletal muscle cells interactions with a perfused muscle-on-chip system

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Introduction: Muscle wasting is a hallmark of chronic obstructive pulmonary disease (COPD). As macrophages, recruited to injured tissues via chemotactic signalling such as the CXCL12-CXCR4 axis, play an important role in skeletal muscle homeostasis and pathology, a role in muscle impairment in COPD is feasible. Methods: We conducted in vitro experiments using the human monocytes cell line THP-1, stimulated or not with LPS (100 ng/mL), and immortalized human skeletal muscle cells. We evaluated the effect of CXCL12 on the adhesion of THP-1 cells to differentiated muscle cells (myotubes) using both classical static cultures and an “in-house” perfused Muscle-on-Chip (MoC) model. We assessed the effect of THP-1 on muscle cells proliferation and differentiation. Results: THP-1 cells were able to proliferate in both growth and differentiation medium of muscle cells and spontaneously adhered to muscle cells upon co-culture. Conditioned medium from LPS-stimulated THP-1, but not from naïve THP-1, significantly enhanced myoblasts proliferation. Co-culture with LPS-stimulated THP-1 altered gene expression of myotubes, including an induction of monocyte chemoattractant protein-1. Pre-incubation of THP-1 with CXCL12 increased the adhesion of THP-1 to myotubes in static conditions as well as in the MoC model. Discussion: Chemotaxis is involved in monocytes recruitment to skeletal muscle cells. In addition, the MoC model supports integration of monocytes to study interactions with skeletal muscle in a perfused setting. Ongoing research will deepen the analysis of the functional impact of monocyte recruitment and polarization on muscle homeostasis in COPD-like conditions.

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