Producing large quantities of muscle fibers has proven to be difficult inside a lab. Until now, researchers have been able to create contracting muscles as well as muscle that is 10 times stronger than our own. albeit in small quantities. Researchers at Brigham and Women’s Hospital (BWH) have just changed all that.
Building muscle cells from precursor cells or culture has been so difficult because muscle cells are unlike other types of cells. In the new study, published this week in Nature Biotechnology, researchers found that by identifying and mimicking important developmental cues, they’d be able to push cells to grow into muscle fibers. This resulted in millimeter-long muscle fibers capable of contracting in a dish and multiplying in huge numbers. The team from BWH knew of previous studies that used genetic modification to create small numbers of muscle cells, but wanted to go beyond that to grow large numbers of cells efficiently.
"We took the hard route: we wanted to recapitulate all of the early stages of muscle cell development that happen in the body and recreate that in a dish in the lab," said corresponding author Dr. Olivier Pourquie, of BWH's Department of Pathology and the Department of Genetics at Harvard Medical School, in a press release. "We analyzed each stage of early development and generated cell lines that glowed green when they reached each stage. Going step by step, we managed to mimic each stage of development and coax cells toward muscle cell fate."
Figuring out just the right amount of differentiation — the specialization of stem cells into certain cell types — in mouse and human pluripotent stem cells, the team found that it was able to create long, mature muscle fibers in a dish. During their experiments, they were also able to culture the stem cells of a mouse with Duchenne muscular dystrophy, and subsequently observed a branched pattern common in muscle fibers with the disease.
The team was also able to produce muscle fibers in these mice with muscular dystrophy by using a more immature type of cell, known as satellite cells. It is unknown, however, whether this method could help humans who suffer from muscular dystrophy, as more research is needed.
"This has been the missing piece: the ability to produce muscle cells in the lab could give us the ability to test out new treatments and tackle a spectrum of muscle diseases," Pourquie said.
In addition to perhaps helping humans with muscular dystrophy, this new method may also help researchers study other muscle diseases, such as sarcopenia, or degenerative muscle loss and cachexia, the wasting away of muscle that typically occurs during severe illness.
Source: Chal, J . Oginum, M. Al Tanoury, Z, et al. Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy. Nature Biotechnology. 2015.