Posted on 12 February 2021
When muscle tissue is injured, muscle stem cells divide to produce new cells capable of forming new muscle tissue and repairing the damage. However, as we age, these stem cells decline in number and become less effective, contributing both to the normal age-related loss of muscle tissue and to severe muscle wasting diseases.
It may be possible to repair damaged muscle by growing these stem cells in the lab and introducing them into the target tissue. However, this approach has proven to be challenging. Here, researchers identify a mechanism by which muscle stem cell division is activated within living muscle tissue, and which could be harnessed in order to induce muscle repair. The research was led by Professor Peter Currie, Director of Monash University’s Australian Regenerative Medicine
The scientists studied the regeneration of skeletal muscle in zebrafish, fast becoming the go-to animal model for the study of stem cell regeneration because the fish are quick to reproduce, easier to experimentally manipulate, and share at least 70 percent of their genes with humans. It is also transparent which allows the scientists to witness the actual regeneration in living muscle.
By studying the cells that migrated to a muscle injury in these fish the scientists identified a group of immune cells, called macrophages, which appeared to have a role in triggering the muscle stem cells to regenerate. “What we saw were macrophages literally cuddling the muscle stem cells, which then started to divide and proliferate. Once they started this process, the macrophage would move on and cuddle the next muscle stem cell, and pretty soon the wound would heal,” Professor Currie said
Macrophages are immune cells that play many key roles in the inflammatory response, such as by ‘eating’ pathogens and presenting their antigens to T and B cells. However, macrophages are also important for repairing tissue damage, as they are capable of suppressing inflammation, clearing debris and promoting healing. There are thought to be multiple types of macrophage, some more geared towards inflammation and some towards healing.
In this study, researchers were not only able to identify the specific type of macrophage involved, but also shed light on the mechanism by which these macrophages promoted stem cell proliferation.
The research team […] found that there were in fact eight genetically different types of macrophages in the injury site, and that one type in particular was the “cuddler”. Further investigation revealed that this affectionate macrophage released a substance called NAMPT. By removing these macrophages from the zebrafish and adding the NAMPT to the aquarium water the scientists found they could stimulate the muscle stem cells to grow and heal – effectively replacing the need for the macrophages.
Importantly recent experiments placing a hydrogel patch containing NAMPT into a mouse model of severe muscle wasting led to what Professor Currie called “significant” replacement of the damaged muscle.
The researchers are now in discussions with a number of biotech companies about taking NAMPT to clinical trials for the use of this compound in the treatment of muscle disease and injury.