Skeletal muscle regeneration is a complex biological process which involves the repair and regrowth of damaged muscle tissue. Understanding its mechanisms is very important in developing effective treatments for injuries and diseases involving the muscle.

What Happens During Skeletal Muscle Regeneration?

The skeletal muscle is one of the three important muscle tissues in the human body, comprising between 30-40% of a person's body mass. They are the muscles that connect to the bones and allow an individual to perform a wide range of movements and functions. Some examples of skeletal muscles are those found in the shoulders, hamstring, and the abdomen.

Skeletal muscles can be damaged by a wide range of conditions, from mild injuries to degenerative diseases such as muscular dystrophy. Fortunately, they have the ability to regenerate after an injury, an efficient stem cell-based repair system which ensures healthy musculature. In order for this repair system to function continuously throughout life, the muscle stem cells must contribute in repairing myofiber and in repopulating the stem cell niche.

The process of regenerating skeletal muscle depends on the collaboration between muscle stem cells (MuSCs) and other cellular elements. When a skeletal muscle is injured, myeloid cells migrate to the wound alongside the activation of MuSCs.

Previous studies revealed the morphological heterogeneity of quiescent MuSCs within the muscle microenvironment. These cells exhibit specialized cellular adhesions and spatial patterns to maintain their quiescent state. However, there is not enough appropriate live animal imaging technology to support the analysis of MuSCs' interaction with myeloid cells.

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Cutting-Edge Microscope Platform

To address this challenge, experts from Hong Kong University of Science and Technology (HKUST) developed a novel platform composed of a dual-laser nonlinear optical microscope. Led by Prof. Qu Jianan and Prof. Wu Zhenguo, the team aimed to investigate the dynamics of MuSCs during the process of muscle regeneration.

The study focuses on the role of myeloid cells, specifically macrophages, in regulating the behavior of MuSC. The research team explored the real-time interactions between non-myogenic cells and MuSCs. It was found that the continuous physical contact between these cell types is not necessary for MuSC activation or cell division.

Macrophages were also found to be unimportant in the activation of MuSCs, but they play a significant role in their proliferation and differentiation during the process of muscle regeneration. Macrophage reduction led to impaired cell division and increased fibrosis during the regenerative process, indicating their stage-dependent role in managing efficient muscle regeneration.

By leveraging the innovative imaging technology, the joint research provided new insights into the complex mechanisms that govern muscle regeneration. The study also challenged the prevailing concept that non-myogenic cells are the major drivers of MuSC activation. Instead, it suggests that MuSCs possess the capacity to sense and respond to regenerative cues that are independent of external signals from non-myogenic cells.

According to Prod. Qu, their findings can contribute to the understanding of the complex dynamics involved in the development of targeted therapeutic strategies for muscle-related disorders.

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