Functioning human muscle cells have been grown in the lab for the first time, marking a leap forward in research on regenerative medicine for injuries and rare muscle-wasting diseases.
A team from Duke University used stem cells placed in a three-dimensional culture to create small clusters of muscle fibers that contract and react to electrical or chemical stimuli, just like native muscle tissue.
The culture was initiated with induced pluripotent stem cells (IPSC), a type of stem cell that can be obtained from the blood or skin of an adult donor. The mature cells are then exposed to certain proteins, causing them to revert into a primordial, undifferentiated state.
In 2015, the same team generated muscle tissue using existing muscle cells, called myoblasts, taken from patients. Unfortunately, this type of parent cell can’t reproduce in great numbers before they begin to break down, limiting the size of the culture.
In the current study, published in Nature Communications, when starting with IPSCs the process was significantly more fruitful. After exposing the cells to a molecule called Pax7, the IPSCs began the process of developing into muscle tissue.
“Starting with pluripotent stem cells that are not muscle cells, but can become all existing cells in our body, allows us to grow an unlimited number of myogenic progenitor cells," said study author Nenad Bursac, professor of biomedical engineering, in a statement. "These progenitor cells resemble adult muscle stem cells called 'satellite cells' that can theoretically grow an entire muscle starting from a single cell."
This approach has the additional benefit of not relying on donated tissue like muscle biopsies. This process can be painful and invasive, and patients with inherited degenerative conditions already experience horrible symptoms and physical impairment.
"When a child's muscles are already withering away from something like Duchenne muscular dystrophy, it would not be ethical to take muscle samples from them and do further damage,” continued Bursac. “But with this technique, we can just take a small sample of non-muscle tissue, like skin or blood, revert the obtained cells to a pluripotent state, and eventually grow an endless amount of functioning muscle fibers to test."
The resulting cell bundles can survive for at least one month in a culture environment and show promise for implantation into a living body. Small clusters of fibers implanted into mice maintained their ability to respond to stimulus and began to integrate into the surrounding tissue by growing blood vessels, surviving for at least three weeks.
This technology is still limited by scale, however, and won’t be able to replace whole muscles anytime soon. Instead, the authors hope the next step will be a combination of targeted replacement in small patches and systemic treatments like gene therapy.