|Stage 1: Macrophages|
The death of muscle fiber and disintegration of the cellular components causes the recruitment of different kinds of white blood cells. Neutrophils are the first ones to respond to the injury. These white blood cells both start the removal of cellular debris and recruit macrophages to the site. Macrophages are the most important white blood cells in relation to muscle regeneration. The first type of macrophages to respond are responsible for ingesting and removing the cellular debris from the dying tissue and secreting factors that induce inflammation. These "inflammatory" macrophages reach their peak 24 hours after injury and then quickly decline. Then a second population of macrophages respond. These "anti-inflammatory" macrophages secrete things to end the inflammation reaction, but also release growth factors that enhance the activity of the satellite cells in the next stage3.
Figure 1: A cross-section of a muscle undergoing a massive immune and inflammatory reaction due to injury. The pink are the muscle fibers while the purple is the immune response and associated cells. (Personal work)
|Stage 2: Satellite Cells|
After injury to muscle tissue, the associated satellite cells quickly multiply. This starts the second day after injury. After the population of satellite cells has massively expanded, the majority of the satellite cells are signaled to begin differentiating into myoblasts, stem cells committed to becoming muscle tissue. The rest remain in the stem cell state to maintain the supply of satellite cells associated with the muscle tissue. The myoblasts fuse together to form new myofibers or sections of myofibers to replace the damaged ones3.
Figure 2: Activated satellite cells within a muscle in response to injury. The red outlines the activated satellite cells and the blue dots are nuclei of various cells (muscle, satellite, and immune). The circular outline of muscle fibers can still be seen in the shape of the satellite cells. (Personal work)
|Stage 3: Maturation|
Immature, regenerated myofibers can be distingushed from mature fibers under a microscope by their smaller size and centrally located nuclei. As the fiber matures the nuclei migrate to the periphery of the myofiber and the fiber increases in size3.
Figure 3: Maturing and mature muscle fibers. The two can be distingushed as the nuclei of the still maturing fibers have not yet moved completely to the periphery of the fibers, while those of mature fibers have. (Personal work)