Researchers have been looking for an easy way to efficiently differentiate stem cells into muscle cells that would be allowable in the clinic, says Suzuki.
A research group at the University of Wisconsin-Madison has discovered a new way to make large concentrations of skeletal muscle cells and muscle progenitors from human pluripotent stem cells. The new procedure that converts stem cells into muscle cells is another step toward moving the use of stem cells into the clinic.
The new method, described in the journal Stem Cells Translational Medicine, could be used to generate large numbers of muscle cells and muscle progenitors directly from human pluripotent stem cells. These stem cells, such as embryonic or induced pluripotent stem cells, can be made into virtually any adult cell in the body.
Adapting a method previously used to make brain cells, Masatoshi Suzuki, an assistant professor of comparative biosciences in the School of Veterinary Medicine, has directed those universal stem cells to become both adult muscle cells and muscle progenitors.
Importantly, the new technique grows the pluripotent stem cells as floating spheres in high concentrations of two growth factors, fibroblast growth factor-2 and epidermal growth factor. These growth factors “urge” the stem cells to become muscle cells.
“Researchers have been looking for an easy way to efficiently differentiate stem cells into muscle cells that would be allowable in the clinic,” says Suzuki. The novelty of this technique is that it generates a larger number of muscle stem cells without using genetic modification, which is required by existing methods for making muscle cells.
“Many other protocols have been used to enhance the number of cells that go to a muscle fate,” says co-author Jonathan Van Dyke, a post-doctoral fellow in Suzuki's lab. “But what's exciting about the new protocol is that we avoid some techniques that would prohibit clinical applications. We think this new method has great promise for alleviating human suffering.”
The new method has a number of advantages including growing the cells in defined supplements without animal products such as bovine serum to enhance clinical safety for the muscle stem cells and growing them as spheres, which allows cells to grow faster than with previous techniques. With the process, 40 to 60 percent of the cells grown are either muscle cells or muscle progenitors, a high proportion compared to traditional non-genetic techniques of generating muscle cells from human embryonic and induced pluripotent stem cells. The researchers hope that further manipulation of the chemical environment of the spheres of stem cells will increase their number.
Suzuki had already demonstrated that transplants of another type of human stem cells somewhat improved survival and muscle function in rats that model amyotrophic lateral sclerosis, a disease that destroys nerves and causes a loss of muscle control. The muscle progenitors generated with Suzuki's new method could potentially play a similar role but with enhanced effect.
The new technique can also be used to grow muscle cells from induced pluripotent stem cells from patients with neuromuscular diseases like ALS, spinal muscular atrophy and muscular dystrophy. Thus, the technique could produce adult muscle cells in a dish that carry genetic diseases. These cells could then be used as a tool for studying these diseases and screening potential drug compounds, Suzuki says. “Our protocol can work in multiple ways and so we hope to provide a resource for people who are exploring specific neuromuscular diseases in the laboratory.”
March 27, 2014
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