Mapping diaphragm stem cell features to treat Muscular Dystrophy

Scientists in recent years have developed processes that allow them to generate cells from a specific type of stem cell. In order to do this, though, they need to know the features and genetic markers of the type of cell that they are trying to create. Researchers have learned much about muscle cells by focusing on the muscles used for movement, such as those in the limbs, but little research has been specifically performed on the diaphragm muscle.

The diaphragm is located immediately below the lungs and is responsible for controlling breathing with each contraction. The location and essential function of the diaphragm makes it more difficult to study, so little is known about diaphragm muscle stem cells. Nevertheless, researchers do realize that diaphragm cells are quite different from the cells in muscles that are used for mobility. This is because the diaphragm contracts with every breath and is not at rest for long periods of time.

One of the major medical conditions that affect the diaphragm is Duchenne Muscular Dystrophy (DMD). This genetic condition causes all of the muscles in the body to slowly deteriorate and lose their ability to function. When the condition of the diaphragm worsens, breathing becomes increasingly more difficult. There is not yet an effective treatment for restoring function to a diaphragm muscle in a patient with DMD.

This research involves two main components. First, researchers will investigate the differences between stem cells in the limbs of mice and stem cells in the diaphragms of mice. They will perform deep sequencing and computational analyses to find the specific genetic differences between the cells. Researchers will also study how the transcription factors present in the stem cells regulate the expression of genes.

Second, the project will apply this new knowledge to create diaphragm stem cells in the laboratory that can be grafted into the diaphragm of a mouse with muscular dystrophy and improve its performance. The stem cells that lack the genetic mutation that causes muscular dystrophy can then operate at full strength and hopefully graft into the diaphragm muscle to strengthen and restore muscle fibers.

This research is timely because DMD affects approximately 1 in 6,000 males in the United States, and there is currently no cure. Only 85 percent of boys with this condition live into their 20s, and only 58 percent live to age 25 or higher, often due to breathing problems. Research that determines how to effectively restore function to the diaphragm muscle can help increase life expectancy and quality of life. The techniques used in this research also have applicability to developing treatments for a wide range of conditions.