Tokyo, Japan – Researchers from Tokyo Metropolitan University have developed a way to treat ageing-related muscular atrophy using regenerative medicine. Conventional methods to implant myoblasts, precursors to muscle fiber, required prior scarring for the new cells to graft properly. By adding extracellular matrix (ECM) fluid into the implant, the team successfully grafted myoblasts onto healthy muscle in mice. Their technique opens the way for using implantation to treat unscarred muscle atrophied by ageing.
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.
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 extracellular matrix (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.
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.
This work was supported by a Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for JSPS Fellows (Grant number 24KJ1872), the Japan Science and Technology Agency via the Fusion Oriented Research for Disruptive Science and Technology Program (JST FOREST Program Number JPMJFR205K), a Tokyo Metropolitan Government Advanced Research Grant (R2-2), TMU Strategic Research for Innovative Research Projects, and TMU Young Selection Research Support for Promising Research.
