A Scar-Free Approach to Combat Age-Related Muscle Atrophy

A new regenerative medicine technique using extracellular matrix successfully grafts myoblasts onto healthy muscle, increasing muscle mass by 10%.

Scientists at Tokyo Metropolitan University have found a method to treat age-related muscle atrophy using regenerative medicine. Traditionally, implanting myoblasts, the precursors to muscle fibers, required prior scarring to ensure proper cell grafting. However, by introducing extracellular matrix (ECM) fluid into the implant, the team was able to successfully graft myoblasts onto healthy muscle in mice. This breakthrough could pave the way for implanting treatments for muscle atrophy caused by aging without the need for scarring ().

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The Impact of Age-Related Muscular Atrophy

Age-related muscular atrophy in skeletal muscle can have a devastating impact on people’s quality of life, as well as make them more susceptible to a wide range of diseases. Prevention regimens like resistance exercise and the right diet are vital from a public health perspective but are hardly a complete solution given the scale and immediacy of this societal issue.

That is why researchers have been seeking effective treatments for muscular atrophy. A promising avenue for this work is regenerative medicine, using stem cells to create and augment existing muscle. However, it turns out that this is not so easy. Simply implanting myoblasts, precursors to skeletal muscle, simply does not solve the problem. For the most part, the new cells do not graft into the existing muscle and simply die out. Interestingly, this is not the case when there is an injury present, or a patient has specific diseases like Duchene muscular atrophy, where muscle fibers are collapsing faster than they are being repaired. The common feature is that the muscle is in a “repair mode,” when stem cells in the skeletal muscle tissue called satellite cells are in an activated state, secreting the right signals to enable cell grafting to occur.

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Incorporating Extracellular Matrix for Better Grafting

Now, a team led by Associate Professor Yasuro Furuichi from Tokyo Metropolitan University has used this insight to develop a new way of implanting myoblasts. Instead of simply injecting myoblasts by themselves, they added some ECM to the injection fluid, the “scaffold” that helps keep cells in place in our bodies. Repair of the ECM is a big part of the process of muscle repair; the team reasoned that the ECM itself may contain some of the right ingredients to trigger the successful grafting of myoblasts into skeletal muscle fiber.

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Balancing ECM and Myoblast Concentration

Through experiments on mice, it was found that higher amounts of ECM together with myoblasts lead to higher amounts of myoblasts being grafted into unscarred tissue. This wasn’t without its issues; beyond a certain point, fibrils of collagen began to intrude into the new, healthy tissue (fibrosis). The team was able to solve this by also increasing the concentration of cultured myoblasts in the implant. To date, they have been able to boost the mass of a mouse’s tibialis anterior (in the lower leg) by a massive ten percent.

Though they are yet to find out what ingredient of ECM is helping muscle cells incorporate properly, this is a big step forward for using regenerative medicine to treat a universal public health issue.

Reference:

Achieving myoblast engraftment into intact skeletal muscle via extracellular matrix - (https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1502332/full)

Source-Eurekalert

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