Another step forward for muscle stem cells

Published Date
22/12/2008
Author
Super Administrator
Category
Research

Research lead by Amy J. Wagers at Harvard University, USA, has shown promise for isolating muscle stem cells, a step towards making cell transplantation a possible treatment for muscle diseases.

Contents:

What did the researchers at Harvard find?

Dr Wager’s group of researchers refined a technique to purify satellite cells from adult mouse muscles which are thought to have some stem cell characteristics. Satellite cells are the cells in muscle known to carry out muscle growth, repair, and regeneration. The researchers used a technique called ‘flow cytometry’ to isolate these satellite cells. Five proteins on the surface of the cells were used to help identify the cells.

A mouse model for Duchenne muscular dystrophy was used to test the isolated satellite cells. Muscle satellite cells isolated from healthy mice were transplanted into mice that have a mutation in the dystrophin gene. Four weeks after the transplant, the muscles of the transplant recipients were analysed.

The transplanted satellite cells were shown to repair the dystrophic muscle and start making dystrophin. The strength of the transplanted muscle was also shown to improve by more than five times. Remarkably the transplanted satellite cells survived in the recipient mice for at least four months, and were able to carry out more repair when muscles were later damaged again. The authors claim that the efficiency of the transplant was five to 40 fold higher than previously published studies where the cells were purified in a different way.

What does this mean for muscular dystrophy?

Although this shows promise for the therapy of human muscle disease, there are many practical hurdles. In humans, avoiding immune rejection of transplanted cells and distributing the cells evenly throughout the muscles of the body would be a major challenge. This paper does however give us valuable information on potential methods for the isolation of muscle stem cells, which will allow us to learn more about these vital cells.

Statement by Dr Peter Zammit, King’s College London:

Any research that further characterises the molecules expressed by satellite cells, and provides techniques to efficiently isolate them from muscle, is of obvious interest. It will be important to determine whether the criteria used in this paper to isolate satellite cells from mouse, also apply to man.

Statement by Dr Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign:

Increasingly more research is being carried out to further the understanding of stem cell biology. The results reported by Dr Amy J Wagers and her team show that it is possible in an animal model to isolate muscle stem cells from a healthy adult mouse and transplant them successfully into a mouse with muscular dystrophy. Although stem cell technology is still in it’s in infancy this is another step towards developing this technology into a viable treatment for people with muscle disease.

Background information

What are stem cells?

Stem cells are essentially a repair system in the body. They are unspecialised cells which, given the right signals, can become any of the specialised cells of the body such as muscle or skin. Another special feature of stem cells is that they can divide in unlimited numbers to replenish themselves. It is known that early embryos contain stem cells, but more recently it has been found that most tissues in the adult contain small numbers of stem cells. These cells spring into action to repair damage when it occurs. The challenge now for scientists is to find ways of identifying and isolating stem cells from adult tissues.

What is known about muscle stem cells?

It has been known since the 1960s that cells called satellite cells are present in muscle for repair purposes. Studies by several groups in recent years have identified cells amongst these satellite cells which seem to behave like stem cells, and identified some of their unique characteristics. Previous attempts to transplant satellite cells from one mouse to another have shown that the process is inefficient, with very few muscle cells growing. In part, this is thought to be because the technique used to isolate them was not optimal. Researchers have been working on better techniques to purify muscle stem cells to improve the efficiency of transplants, with some success. In particular stem cells have been selected on the basis of their behaviour in culture, such as their ability to survive and multiply for long periods of time. In one study, these cells have been found to be approximately five times more efficient than impure satellite cells.

What causes Duchenne muscular dystrophy?

Duchenne muscular dystrophy is an inherited disease which causes severe muscle wasting. It occurs in one out of every 3,500 newborn boys. Duchenne muscular dystrophy is caused by a genetic mutation that results in the absence of the functional form of a muscle protein called dystrophin. This protein is an important component of the structure of muscle. When dystrophin is missing or non-functional, muscle tissue starts to degenerate. Muscle satellite cells initially play a role in repairing this degeneration but eventually fail. Although this research focuses on Duchenne muscular dystrophy, it is thought that stem cells may be used to treat many different types of muscle diseases in the future.

Further information and links

You can read more about the report on the BBC website.

The original paper called “Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles” was published in the Cell journal. It is not freely available and is written in technical language.

The Muscular Dystrophy Campaign currently supports research projects into muscle stem cells, including work carried out by Dr Peter Zammit at King’s College London and Dr Jenny Morgan at Imperial College London. For more information about these research projects, visit our current research grants.

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