Muscle stem cells are a fickle group. Shortly after they're removed from their native environment (snuggled along the length of our muscle fibers), they begin to lose their potency and become increasingly less stem-like. This makes maintaining them in the laboratory a tricky task.
Now neurologist Thomas Rando, MD, PhD and former postdoctoral scholar Marco Quarta, PhD, have found a way to soothe the homesick cells by crafting artificial muscle fibers and a custom-made broth that mimic the conditions of natural muscle. Their work was published yesterday in Nature Biotechnology.
As I described in our release:
Keeping muscle stem cells happy in the lab is an important step toward potential therapies for conditions like muscular dystrophy and toward regenerating missing muscle after an injury. One day researchers would like to be able to remove a patient’s own muscle stem cells, correct any genetic deficiencies if necessary, and then transplant the cells back into the patient to regenerate healthy muscle tissues. This is not possible if the stem cells lose their ability to regenerate new muscle.
Rando and Quarta compared the gene expression profiles of freshly isolated mouse muscle stem cells with that of cells that had been maintained in the lab for a period of time. Once they identified genes specifically expressed in fresh stem cells, they worked to concoct a broth of nutrients that kept the cells potent. They then went one step further, collaborating with researchers in the laboratory of Sarah Heilshorn, PhD, in Stanford's Department of Material Science and Engineering, to generate artificial muscle fibers out of collagen -- a naturally occurring and biocompatible molecule that can mimic the elasticity of real fibers.
From our release:
When the researchers applied muscle stem cells to the artificial collagen fibers, the cells quickly “homed” to places similar to those in which they would be found in real muscle. When maintained in the specially concocted quiescence broth, the cells appeared snug and happy along the collagen fibers. Furthermore, transplantation experiments indicated the muscle stem cells maintained their potency over several days and were able to quickly engraft and begin making new tissue in recipient animals.
The researchers also repeated the experiment using human muscle stem cells maintained under similar conditions and then transplanted into laboratory mice.
“This artificial niche, plus bathing the cells in the appropriate factors, allows us to maintain the cells in a highly potent, quiescent state,” said Rando. “Now we can genetically engineer stem cells, transplant them back into the animal and see that they are effective in engrafting and making new tissue.”
Previously: "Alert" stem cells speed damage response, say Stanford researchers, Tick tock goes the clock – is aging the biggest illness of all? and Stem cells implicated in Duchenne muscular dystrophy
Photo of muscle stem cell on artificial fiber courtesy of the Rando laboratory