A group of researchers in the USA has used a screen in zebrafish cells to identify three factors that promote muscle tissue formation in human induced pluripotent stem (iPS) cells. This is the first time researchers have been able to promote muscle cell formation from this type of stem cell using such a simple technique. The discovery could pave the way for stem cell transplantation as a therapy for muscular dystrophies and related neuromuscular conditions in the future.
What did the research show?
Using a screen in embryonic stem cells from zebrafish, researchers discovered six factors that promote muscle formation, which could be used to grow stem cells suitable for transplant. The zebrafish cells were genetically modified so that the researchers could trace their development into muscle tissue. By treating the cells with a number of different compounds, factors that promote muscle cell formation could be detected, and after testing 2,400 compounds, six were identified that drove the development of stem cells to muscle cells.
Two major obstacles to stem cell therapies are getting sufficient cells to transplant and controlling their development into muscle cells. Finding factors that can increase stem cell numbers and push them towards becoming muscle cells as opposed to other types of cell is an important step towards overcoming these challenges.
The researchers found that one of the six identified compounds, called forskolin, increases the division of muscle stem cells, called satellite cells, grown in the laboratory. The cells increased in number, retained their important stem cell characteristics and were successfully transplanted into mice.
A cocktail of three identified factors, including forskolin, was tested on human iPS cells in the laboratory. iPS cells are similar to embryonic stem cells but are made in the laboratory by genetically reprogramming adult cells; researchers hope this could be a useful source of stem cells. When treated with the cocktail, iPS cells developed into satellite cells and muscle cells, indicating a far more efficient way of generating satellite cells in the laboratory than traditional methods, which are lengthy and often require genetic manipulation. When the satellite cells were transplanted into mice with injured limb muscles, the transplanted cells showed typical properties of satellite cells: repairing muscle damage and repopulating the stem cell pool, which acts as a store of dormant satellite cells that become activated when muscle tissue is damaged.
This research is an important step towards the development of stem cell therapy for people with muscular dystrophy and other related neuromuscular conditions.
It demonstrates a simple method of generating large numbers of satellite cells in the laboratory. Satellite cells are the key stem cells in adult muscle, making them an attractive choice for transplantation in people with neuromuscular conditions. A big challenge is producing enough cells for transplantation, but this new method could help researchers overcome this hurdle.
However, the technique is still in the early stages of development, being tested in animals, and more research is needed before it can be tried in humans. Particularly, it is crucial to ensure the behavior of the transplanted stem cells can be controlled, otherwise there is a risk they could become cancerous in the body.
Induced pluripotent stem (iPS) cells are adult cells, eg from skin, that have been manipulated in the laboratory to have the properties of embryonic stem cells. The cells undergo ‘genetic reprogramming’ by being forced to turn on specific genes that take them back to an embryonic stem cell-like state. Similar to cells from an embryo, the cells are capable of dividing to increase their numbers and of developing into any type of cell.
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