Forever young: Scientists figure out how to renew muscle tissue
MUSCLE tissue can be renewed by chemically resetting its biological clock to an earlier stage of development, a study has shown.
Scientists believe the technique may pave the way to reversing muscle loss due to disease or natural ageing.
It may also be extended to repairs of other kinds of tissue, such as brain and liver.
US researchers used molecular signals to separate mature muscle tissue into individual "progenitor" cells called myoblasts.
These were then successfully used to repair the damaged muscles of injured mice.
"The research opens the door to the development of new treatments to combat the degeneration of muscle associated with muscular dystrophy or ageing," said study leader Dr Irina Conboy, from the University of California at Berkeley.
Crucially, the technique does not rely on the creation of "pluripotent" stem cells - immature cells that can differentiate into virtually any kind of tissue.
Previous attempts to regenerate muscle using pluripotent embryonic stem cells or reprogrammed adult cells have led to uncontrolled growth and tumours.
The new approach, described in the journal Chemistry & Biology, avoids this danger by not returning cells to an embryo-like state through genetic reprogramming.
Instead, it uses specific inhibitor chemicals that coax muscle back one stage of of development but no further.
Skeletal muscle tissue is composed of elongated bundles of "myofibres" composed of individual myoblasts that have fused together.
The Berkeley scientists succeeded in returning the myofibres back to their previous state as separate myoblast cells.
"Muscle formation has been seen as a one-way trip, going from stem cells to myoblasts to muscle fibre, but we were able to get a multi-nucleated muscle fibre to reverse course and separate into individual myoblasts," said Dr Conboy.
"For many years now, people have wanted to do this, and we accomplished that by exposing the tissue to small molecule inhibitor chemicals rather than altering the cell's genome (genetic code)."
Under normal conditions, muscle is continually destroyed and replaced with new tissue generated by stem cells.
This is how people build up their muscles through exercise. Lifting weights, for instance, damages muscle tissue and triggers repairs that make it stronger.
But sometimes, as occurs in people with Duchenne muscular dystrophy, the repair process stops working. Natural ageing also makes it harder to replace lost muscle tissue.
The scientists turned the clock back on muscle fibres using one chemical that transmits signals for cell division, and another that prevents cells dying.
"We basically brainwashed the cells to go into the cell cycle, to divide, and also not die in the process," said Berkeley bioengineer Dr Preeti Paliwal.
Exposing muscle fibres to the chemicals for 48 hours was long enough for them to split into individual cells.
The scientists used a green fluorescent genetic label to trace the origin of the myoblast cells. This proved they came from mature muscle tissue, and were not generated by stem cells.
To test the viability of the newly created myoblasts, the scientists cultured them in the laboratory and watched them grow, multiply and fuse to form myofibres.
Myoblasts were then injected into live mice with damaged muscles.
"After two to three weeks, we checked the muscle and saw new muscle fibres that glowed green, proving that the progenitor cells we derived from mature muscle tissue contributed to muscle repair... in mice," said Dr Paliwal.
Next the researchers plan to test the process on human muscle tissue. They are also searching for other molecules that can help de-differentiate muscle tissue.
Dr Conboy said the same approach might also make it possible to repair other parts of the body, such as the brain or liver. However, it would not work when differentiated cells are missing altogether, as in Type 1 diabetes which results in the loss of insulin-producing pancreatic cells.
She added: "Our approach is not a replacement for pluripotent cells, but it's an additional tool in the arsenal of stem cell therapies."