As of May 25th, 2021, a study has been published in Nature Communications where researchers have showed how the use of certain compounds can help in regeneration of mice’s muscle cells. It can be done by activating muscle cell precursors, also called myogenic precursors. This study is applicable to humans as well as the research provides insights into the underlying mechanisms involved in muscle growth and regeneration. This could one day help both athletes and the elderly to regenerate tissues more effectively as said by Salk Professor, Juan Carlos Izpisua Belmonte, also a Director Author of the article. Their study reveals specific factors that are able to accelerate muscle regeneration and also, the mechanism. The compounds used in the study are often called Yamanaka factors, after the Japanese scientist who discovered them. Yamanaka factors are a combination of proteins (called transcription factors) that control how DNA is copied in order to translate it into other proteins. In laboratory research, they are used to convert specialized cells, such as skin cells, into more stem-like cells that are pluripotent, that is, they have the ability to develop into many different cell types.
The lead author, Chao Wang, a postdoctoral fellow in Izpisua Belmonte's laboratory claimed that, research laboratories have previously showed that these factors can rejuvenate cells and promote tissue regeneration in living animals. But how this happens was not previously known. Muscle regeneration is done by muscle stem cells and satellite cells, which are located in a niche between a layer of connective tissue (basal lamina) and muscle fibers (myofibers). In this study, the team used two different mouse models to identify the muscle stem cells - specific or niche-specific changes after the addition of Yamanaka- Factors. They focused on younger mice to study the effects of age-independent factors.
In the specific myofiber model, they found that the addition of Yamanaka factors accelerated muscle regeneration in mice by reducing the levels of a protein called ‘Wnt4’ in the niche, which in turn activated satellite cells. In the model, Yamanaka factors did not activate satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a critical role in muscle regeneration. A novel gene editing technology has been recently developed that could be used to speed muscle recovery from injury and improve muscle function. Researches informed that they could possibly use this technology to directly lower the Wnt4 level in the skeletal muscles or to block the communication between Wnt4 and muscle stem cells.
