In a surprising discovery with implications for treating muscular dystrophy, researchers at the University of Utah School of Medicine and other institutions have identified a major source of origin for two groups of adult cells that regulate muscle repair.
The researchers found that these muscle repair cells, satellite and side population (SP) cells, arise from somites--transient blocks of tissue in the embryo that give rise to muscle, vertebrae, and the inner layer of skin called the dermis.
The origin of satellite and side population (SP) cells has engendered considerable debate. Published in the Jan. 24 issue of the Proceedings of the National Academy of Sciences, the study shows that a significant number of satellite and SP cells arise from somites. The researchers also found that SP cells originating from somites are much better at forming muscle than SP cells not produced by somites.
"It turns out that an adult muscle cell's capacity to repair damaged muscle is directly related to where it comes from, and this has implications for the potential use of SP cells in repairing muscle in muscular dystrophy patients," said the study's senior author, Gabrielle Kardon, Ph.D., assistant professor at the University's Eccles Institute of Human Genetics.
In adults, damaged or diseased muscle is repaired by populations of adult muscle progenitors, such as satellite and SP cells. Satellite cells are responsible for most muscle repair. However, SP cells, only recently identified, can give rise to satellite cells and also repair damaged muscle.
Some researchers have proposed that SP cells are derived from the bone marrow, while others have suggested that both satellite and SP cells are derived from the somites.
Kardon and colleagues tested whether satellite and SP cells originate from somites by labeling somite cells in developing chicks and mice and following whether the labeled cells ended up as satellite or SP cells.
In chicks, somite cells were labeled by injecting cells with a retrovirus that contains green fluorescent protein (GFP), or by replacing chick somite cells with quail cells.
In mice, somitic cells were genetically labeled. Daughter cells derived from cells expressing the Pax3 gene, a gene expressed in the somites, were labeled with GFP.
In all three experiments, somite cells labeled in chick or mouse embryos gave rise to labeled satellite and SP cells in the adult.
These experiments demonstrate that a significant portion of satellite or SP cells is derived from the somites. However, not all SP cells were derived from the somites, indicating that some may be derived from the bone marrow.
When the researchers went on to compare SP cells derived from somite to SP cells potentially derived from bone marrow, they found that the somite-derived SP cells were much better at making muscle.
Duchenne's muscular dystrophy is caused when the dystrophin gene is defective. Medical researchers have been looking for ways to use SP and satellite cells to deliver healthy copies of dystrophin to the damaged muscle in Duchenne's patients.
Potentially, satellite or SP cells with a healthy copy of dystrophin could be injected into the circulatory system to home to and repair dystrophic muscle.
While satellite cells are highly myogenic (effective in muscle repair) from inside the body, they are inefficient in forming muscle when injected into mice. SP cells have been shown to produce a small amount of muscle when injected into dystrophic mice and may be candidates for delivering dystrophin, according to Kardon.
Using SP cells derived from somites may further increase their efficiency in repairing diseased muscle. But a lot of work remains to be done.
"We need to find highly myogenic cells that can be delivered systemically, such as by injection, and that can both home to and repair all the muscles of the body," Kardon said.