Researchers at Duke University have managed to create functional human muscle tissue using skin cells as the starting point. This research builds on their previous work from 2015, when they grew the first functioning muscle tissue using cells obtained from muscle biopsies.
Being able to create muscle cells using non-muscle tissue opens the door for scientists to grow muscle cells in bulk, provides an easier path to genome editing and gene therapies, offers a supply for basic research studies, and could help create personalized models for rare muscle diseases, leading to better patient outcomes.
Skin cells to muscle cells
In the new study, the researchers used human induced pluripotent stem cells taken from adult non-muscle tissues, in this case from the skin, and reprogrammed the cells back to a pluripotent state, from which they could become any other type of cell. These pluripotent cells were also exposed to the Pax7 molecule, which signaled them to change into muscle cells.
As these cells multiplied, they became very similar to adult muscle stem cells, though not quite as robust. It is worth noting that while previous studies have also done the same thing, no one has previously been able to grow these pluripotent cells into functional skeletal muscle.
A difference in their approach was the unique cell culture and the use of a 3D matrix, which allows the cells to grow and mature significantly faster than traditional 2D approaches in culture. This is a solid step forward on the road to producing skeletal muscle that is identical to its naturally occurring counterpart.
The researchers showed that after two to four weeks in culture, the muscle cells formed muscle fibers that contract in response to external stimuli from biochemical signals and electrical pulses, just like regular muscle tissue does. They also implanted the muscle fibers into adult mice and demonstrated that they survive and function for at least three weeks while integrating with the native tissue, including vascularization.
Despite not being as robust as resident muscle tissue, this newly grown tissue holds potential that its older counterpart does not. The researchers showed that the pluripotent stem cell-derived muscle fibers develop reserves of satellite-like cells; these are required for adult muscle to repair damage. The muscle tissue developed from a biopsy in their previous study had less of these reserve repair cells than the pluripotent stem cell-derived muscle cells in this study.
The technique they used is also able to grow far more muscle cells from a smaller initial batch than the biopsy method, making it considerably more efficient. This has implications for mass production and reducing costs, which is an absolute must for getting these advanced technologies into the mainstream more quickly.
Both of these advantages suggest that this new approach could be used for regenerative therapies and personalized health care. The researchers are now refining the technique to create more robust muscles and using it to develop new, customized models of rare muscle diseases.
This is yet another step forward for tissue engineering and the refinement and application of practical therapies that could help address diseases. Such a technique might be combined with gene therapies to potentially correct genetic malfunctions in induced pluripotent stem cells taken from a patient with a disease like Duchenne muscular dystrophy, then used to create patches of healthy functional muscle.
It also has implications for age-related diseases such as sarcopenia, which occurs when aging causes muscle wastage, leading to frailty and the loss of independence. We look forward to more progress on this front in the near future.
 Lingjun Rao, Ying Qian, Alastair Khodabukus, Thomas Ribar and Nenad Bursac. Nature Communications, January 2018 Engineering Human Pluripotent Stem Cells Into a Functional Skeletal Muscle Tissue. DOI: 10.1038/s41467-017-02636-4
 Madden, L., Juhas, M., Kraus, W. E., Truskey, G. A., & Bursac, N. (2015). Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs. Elife, 4, e04885.