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Researchers at the University of Texas Southwestern Medical Center (UT Southwestern) have used embryonic stem cells from mice to grow muscle cells. These same cells, injected into mice with a mild form of muscular dystrophy, formed healthy, functional muscle fibers at the site of deteriorating tissue. Scientists say that the research, while still in its early stages, could eventually lead to a cell-based therapy for patients with muscular dystrophy and other muscle-related diseases. The research was recently published in the online edition of Nature Medicine.

According to the Muscular Dystrophy Association, about 250,000 people in the United States have some form of the disease. The most well known, Duchenne muscular dystrophy, is caused by a genetic mutation that disrupts the formation of dystrophin, an important protein involved in the formation of muscle cells. In the absence of dystrophin, muscles are unable to regenerate, and they gradually weaken and waste away. Eventually, the deteriorated area is taken over by fat and connective tissue.

Rita Perlingeiro, assistant professor of developmental biology at UT Southwestern, says that embryonic stem cells may be the key to reversing muscular dystrophy’s debilitating effects. The advantage lies in the cells’ pluripotency–the ability to transform into any mature cell, be it bone, muscle, or cartilage. However, many researchers have found it difficult to direct every stem cell in a culture to form a specific type of cell. In lab experiments, scientists often end up with a mixture of cells that, when injected into an animal, form large clusters resembling a tumor.

So Perlingeiro and her team set two main goals: to find the right set of cues to convert embryonic stem cells into muscle cells, and to look for ways to isolate muscle cells from the rest of the culture medium, in order to inject a dose of pure muscle cells into a mouse model.

In normal embryologic development, stem cells turn into various tissue and bone, depending on a combination of molecular and genetic signals. In the case of muscle cells, past research has shown that the gene Pax-3 is essential in pointing stem cells down the path of muscle formation. With this knowledge, Perlingeiro and her team grew mouse-derived embryonic stem cells in a culture dish, then genetically manipulated the solution to overexpress Pax-3. They found that, compared with mixtures without Pax-3, a significant number of stem cells exposed to the activated gene formed muscle cells.

However, not all of the cells turned into muscle, and when the team injected the solution into a mouse with a mild form of muscular dystrophy, the mixture caused tumors to form. The team then focused on developing an identification process that would make muscle cells stand out from the rest of the solution. Once again, Perlingeiro looked to basic developmental research and found that, during normal muscle formation in the embryo, stem cells that become very early versions of muscle cells display certain surface molecules, or markers. The team repeated the first phase of its experiment, exposing embryonic stem cells to Pax-3, and looked for the telltale markers indicating muscle cells. The researchers then isolated these cells, creating a solution that consisted solely of muscle cells.

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Credit: University of Texas Southwestern Medical Center

Tagged: Biomedicine, stem cells, disease

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