Scientists have cultivated human muscle stem cells capable of renewing themselves and repairing muscle tissue damage in mice, an advance that may lead to new ways of treating wasting disorders in people.
In the research, published earlier this month in the journal Cell Stem Cell, scientists genetically reprogrammed lab-cultured human skin cells into a more primitive state in which they can develop into almost any type of cell in the body.
These primitive cells – known as induced pluripotent stem (IPS) cells – were mixed with a solution of standard cell growth factors and nutrients to nudge them to differentiate into specific cell types, say the researchers, including those from Johns Hopkins University in the US.
Previous studies have demonstrated that IPS cells can be transformed into units such as skin or brain cells. But scientists said turning these primitive state cells into self-renewing stem cells for a particular organ has been difficult.
In the study, scientists coaxed IPS cells to turn into muscle stem cells and injected these into mouse muscles.
They found that the injected cells moved to an area of the muscles known as the niche – where other natural muscle stem cells are typically found – and stayed there for more than four months.
Scientists then determined if the muscle stem cells would repair damaged tissue in two ways.
In one method, researchers transplanted the muscle stem cells into mice genetically engineered and bred without an immune system to avoid rejection of the transplanted cells.
They then exposed the rodents to a muscle-degrading toxin and radiation to eliminate muscle stem cells already existing within the mouse.
At the site of the toxin and radiation damage, scientists found that the transplanted human muscle stem cells developed into myoblasts, which are undifferentiated cells capable of giving rise to muscle cells.
This kind of muscle construction cell repairs damage by fusing together and developing the microfibers that characterise normal muscle, they noted.
Researchers also discovered that some of the transplanted stem cells migrate to the niche and behave like muscle stem cells naturally found within the mouse.
In another method, they injected the stem cells into mice genetically engineered with a mutation that causes Duchenne muscular dystrophy – a muscle-wasting disorder in mice and humans.
Here too scientists found that the stem cells traveled to the muscle niche area, and over several months the mice were able to run twice as far on mini treadmills than untreated mice, a measure of muscle strength.
“These muscle stem cells could potentially be developed as treatments for many types of muscle disorders,” study co-author Gabsang Lee from Johns Hopkins Medicine said in a statement.
Dr Lee is also co-founder of Vita Therapeutics Inc, a Baltimore-based cell engineering company that hopes to bring muscle stem cell treatments to market for muscle wasting disorders, including muscular dystrophy.
In future studies, scientists plan to study the use of the cells in mouse models of other muscle-related conditions.
The fate of the injected stem cells in the mice also needs to be closely studied, they said.
Researchers believe further studies may lead to potential applications in sports medicine, trauma, and age-related muscle loss.
