One of the many effects of ageing is loss of muscle mass, which contributes to disability in older people. To counter this loss, scientists at the Salk Institute are studying ways to accelerate the regeneration of muscle tissue using a combination of molecular compounds that are commonly used in stem-cell research.
In a study published in Nature communication, these investigators showed that using these compounds increased the regeneration of muscle cells in mice by activating the precursor of muscle cells called myogenic progenitors. Although more work is needed before this approach can be applied in humans, the research provides insight into the underlying mechanism related to muscle regeneration and growth which could one day help athletic as well as ageing adults regenerate tissue more effectively.
“Loss of these progenitors has been connected to age-related muscle degeneration,” said Salk Professor Juan Carlos Izupisua Belmonte, the paper’s senior author. “Our study uncovers specific factors that are able to accelerate muscle regeneration as well as revealing the mechanism by which this occurred”.
The compounds used in the study are often called Yamanaka factors after the Japanese scientist who discovered them. Yamanaka factors are a combination of protein (called transcription factors) that control how DNA is copied for translation into other protein in lab research, they are used to convert specialized cells, like stem cell into more stem cell-like cells that are pluripotent which means they have the ability to become many different types of cells.
“Our laboratory previously showed that these factors can rejuvenate cells and promote tissue regeneration in live animals,” said first author Chao Wang, a postdoctoral fellow in the Izupisua Belmonte lab“ but how this happened was not previously known”.
Muscle regeneration is mediated by muscle stem cells, also called satellite cells. Satellite cells are located in the niche between a layer of connective tissue (basal lamina) and muscle fibres (myofibers). In the study, the team used two different mouse model to pinpoint the muscle stem cell-specific or niche-specific changes following the addition of Yamanaka factors. They focused on younger mice to study the effect of factors independent of age.
In the myofibers-specific models, they found that adding Yamanaka factors, accelerated muscle regeneration in mice by reducing the level of a protein called Wnt4 in the niche, which in turn activated the satellite cells by contrast in the satellite-cell-specific model. Yamanaka factors did not active satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a vital role in muscle regeneration.
According to Izupisua Belmonte, who holds the Roger Guillemin Chair, the observation from this study could eventually lead to new treatment by targeting Wnt4.
“Our laboratory has recently developed novel gene-editing technologies that could be used to accelerate muscle recovery after injury and improve muscle function”, he said. “We could potentially use this technology to either directly reduced Wnt4 levels in skeletal muscle or to block the communication between Wnt4 and muscle stem cells”.
The investigators are also studying other ways to rejuvenate cells including using MRNA and genetic engineering, these techniques could eventually lead to new approaches to boost tissue and organ regeneration.
By: Peace Chigozie