Our skeletal muscles, which link to bones and enable us to move, have a remarkable ability to regenerate after they've suffered an injury. Scientists have now developed a cutting edge microscopy tool that has enabled them to visualize the process of muscle regeneration, which requires muscle satellite cells (MuSCs). This technology has provided new insights into MuSC function as muscles are repaired, which could help researchers create better therapeutics for diseases that affect muscle. The findings have been reported in Science Advances.
When muscles are damaged, MuSCs are activated, and myeloid cells move to the site of the injury. The MuSCs grow and differentiate into cells called myocytes; they then fuse to injured fibers, or with one another to create new fibers. The mechanisms underlying MuSC activation have been unclear, however.
In this study, the researchers integrated second harmonic generation and two-photon excited fluorescence into a "multimodal nonlinear optical microscope system." This tool enabled them to visualize the complex interactions between various cell types as muscles as regenerating.
The investigators determined that MuSCs are able to detect and respond to regenerative signals, which can happen without any input from non-myogenic cells. This contradicts previous research that has suggested that non-myogenic cells are related to MuSC activation. But physical contact between non-myogenic cells and MuSCs was not required for MuSC activation or cell division. The research indicated that non-myogenic cells do, however seem release signals that help regulate MuSC proliferation.
The study also suggested that macrophages are also not needed for MuSC activation, but macrophages are critical to the growth and differentiation of MuSCs while muscles are regenerating. When muscle regeneration occurred in the absence of macrophages, cell division was disrupted and fibrosis, or scarring, increased.
“Our findings contribute to the understanding of the complex dynamics underlying muscle regeneration processes and hold significant implications for the development of targeted therapeutic strategies for muscle-related disorders," said Professor Qu Jianan of The Hong Kong University of Science and Technology (HKUST).
"By combining technical skills in advanced imaging technology with biological expertise, we achieved a comprehensive understanding of the intricate cellular interactions involved in [skeletal muscle regeneration],” said Professor Wu Zhenguo, also of HKUST.
Sources: HKUST, Science Advances
