Can We Improve Adult Regeneration By Learning From Fetal Muscle Stem Cells?

Fetal muscle stem cells have extraordinary regenerative capabilities compared to adult ones, but how do they do it? They remodel their environment to aid repair

You don't need to be a scientists to know muscle repair declines with age, but fetal stem cells may offer a solution - helping us to boost stem cell activity and enhance rejuvenation. 

A wasting problem

The dangers of muscle atrophy can't be overstated in the elderly. Muscle wastage contributes to a huge drop in quality of life for many people, and while exercises and diet can delay decline to an extent, we need more potent solutions to the problem. We shouldn't forget there are also many people living with currently debilitating muscular dystrophies that could benefit from such a treatment too. 

"We found that fetal MuSCs remodel their microenvironment by secreting specific proteins, and then examined whether that same microenvironment can encourage adult MuSCs to more efficiently generate new muscle. It does, which means that how adult MuSCs normally support muscle growth is not an intrinsic characteristic, but can be changed" 

The environment is the key

The latest research published in Cell Reports highlights key differences between fetal and adult stem cells. As the fetal cells mature they change priorities - shifting to a focus on repairing existing muscle over the creation of new tissue. As these cells change, the environment around them changes too. While adult muscle stem cells (MSCs) work pretty well when you're young and relatively sprightly, atrophy eventually eclipses their ability to recuperate lost muscle.

The researchers discovered that fetal MSCs are more interactive with their environment and the neighbouring extracellular matrix; a gel like mixture containing proteins and factors that surrounds cells. They appeared to secrete specific proteins in comparison to their adult counterparts, so the team theorised that placing adult MSCs in a similar environment might improve function. They were right. 

An intriguing finding

A cell's local environment plays an important role in determining its behaviour Credit: Klingberg et al. (2014) J. Cell Biol. 207:283-297

When placed in a micro-environment similar to that of fetal MSCs, adult ones displayed improved regenerative capabilities. This is really important, because it illustrates that loss of regeneration probably isn't due to an intrinsic problem within the stem cell themselves, but within their environment. Other research is also suggesting multiple stem cell niches across the body could be vulnerable to these changes too, but that the stem cells themselves may behave youthfully again if in a different chemical environment. This opens the door to potential new therapies which could mould this environment back to a 'younger' format. 

"Our findings fit with the growing appreciation of the importance of a cell's structural and biochemical surroundings in influencing cellular behavior. Managing the microenvironment is an emerging approach to treat many diseases, from cancer to cardiovascular disease to neurodegeneration. We're excited about the implications of our research for treating muscle diseases, and look forward to applying our conclusions toward development of therapies"

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