There are hundreds of individually-named skeletal muscles in the human body, each positioned in a specific place to allow the body to move in countless different ways. When muscles lose function due atrophy or injury, motor function decreases, and it can diminish an individual’s quality of life. A new paper published in EMBO Molecular Medicine describes a study that used stem cells to grow leg muscle tissue in a dish, which proved to be functional after it was grafted into a mouse. In the future, this technique could be applied to humans, providing tissue transplants to treat muscular dystrophy or a number of other muscle-related diseases.
The cellular basis of the muscle tissue are mesoangioblasts, which are undifferentiated cells capable of becoming tissues of the endothelium (vessels) or mesoderm (muscles). The cells were provided with nutrients and growth factors in a dish on a hydrogel matrix, and were induced into becoming muscle tissue. Ultimately, the researchers produced a muscle that resembled tibialis anterior, a muscle that stabilizes the ankle during locomotion.
The researchers then grafted the manufactured muscle into a mouse whose tibialis anterior had been injured. Quite happily, the muscle transplant was a resounding success.
“The morphology and the structural organization of the artificial organ are extremely similar to, if not indistinguishable, from a natural skeletal muscle,” senior author Cesare Gargioli of Tor Vergata Rome University said in a press release.
Muscle tissue grown in vitro. Image credit: Fuoco et al., 2015/EMBO Molecular Medicine
One of the biggest challenges of growing muscles in vitro is that there is not a circulatory system capable of delivering oxygen and nutrients throughout the muscle as it gets larger. While tissue grafts would benefit the millions of Americans living with muscular dystrophy, the logistics of creating these muscles has been problematic. Even if the tissue is able to grow well in vitro, transplant typically fails because the recipient isn’t able to generate the nerves and blood vessels necessary to sustain the new muscle. However, using the mesoangioblasts allows the tissue to develop the necessary vessels as well, improving the odds of success for the developing muscle.
Because developing a replacement muscle large enough to be grafted into a human is considerably more challenging than making one for a mouse, the researchers have a different growth method in mind. Rather than growing the tissue in a dish and transplanting it into a human later, the new muscle would be grown right alongside the damaged tissue in the body. This approach would signal the body to produce new nerves and vessels as the tissue is growing, aiding in the ultimate success of the procedure. This technique is still a long way off from being used in humans, but further tests with larger animal models would provide the proof of principle needed in order to proceed in that direction.
“While we are encouraged by the success of our work in growing a complete intact and functional mouse leg muscle we emphasize that a mouse muscle is very small and scaling up the process for patients may require significant additional work,” co-author Giulio Cossu of University College London concluded.