New Advances in Regenerative Medicine using Zebrafish

Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues. The promise of regenerative medicine, including gene therapy, stem cell treatments, and the repair or regeneration of various tissues and organs, has been discussed for more than two decades. Stem cells can be guided into becoming specific cells that can be used to regenerate and repair diseased or damaged tissues in people.

Satellite cells are one type of stem cell that occupies a specific niche within a differentiated tissue. Decades of research have revealed this system’s extraordinary capacity to effectively coordinate muscle repair in response to a wide variety of injuries. Despite this demonstrated regenerative capacity, transplantation of isolated muscle stem cells has yet to provide therapeutic impact, and pro-regenerative treatments that stimulate muscle stem cells are entirely lacking.

Researchers at Monash started by studying the cells that migrated to injury sites in zebrafish. They developed a zebrafish muscle injury model to view satellite cell interactions within the injury site, in real-time, throughout the repair process.

They discovered eight genetically distinct macrophages—only one of which seemed to be involved in the regeneration of muscle stem cells. These cells release Nicotinamide phosphoribosyltransferase (NAMPT/Visfatin/PBEF). The team later removed the macrophages from the zebrafish and then added NAMPT to the aquarium water.

According to the researchers, muscle stem cells started to grow and promote healing, showing that the protein took over for the missing macrophages.

Ratnayake, Dhanushika, et al. did further studies with NAMPT, which included placing patches that contained the protein into mouse models of muscle-wasting disease. They observed significant muscle healing showing that NAMPT-based therapies could help treat a range of conditions, including muscular dystrophy, limb injuries, and muscle wasting due to aging.

READ MORE:

Ratnayake, Dhanushika, et al. “Macrophages provide a transient muscle stem cell niche via NAMPT secretion.” Nature 591.7849 (2021): 281-287.

Zebrafish reveal regenerative protein that could inspire new treatments for muscle-wasting diseases and aging.

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