Scientists have made a breakthrough in regenerative medicine by fully restoring a degenerated organ in a living animal for the first time.
A team from the Medical Research Council (MRC) Centre for Regenerative Medicine, at the University of Edinburgh in the UK, reconstructed the thymus of aging mice. They report their findings in the journal Development.
The thymus is a glandular structure that functions as part of the body’s immune system by creating T cells – the type of white blood cell that is essential for fighting infection. Located in the front of the heart, the thymus is the first organ to deteriorate as we age.
Scientists have attempted to regenerate the thymus before, using sex hormones. But using this technique, the thymus only temporarily regenerated with limited functional recovery.
The MRC scientists were able to rebuild the thymus by reactivating a natural mechanism in the mice that shuts down as part of the aging process.
To do this, they genetically modified mice to enable them to increase levels of a protein called FOXN1. This protein helps control how genes in the thymus are activated. Using chemical signals to stimulate the increase of FOXN1 in the mice, the scientists were able to instruct immature cells in the thymus – similar to stem cells – to “switch on.” Once activated, the immature cells rebuilt the organ in the older mice.
Ultimately, the MRC researchers hope that a similar process can be applied to humans.
“By targeting a single protein, we have been able to almost completely reverse age-related shrinking of the thymus,” Prof. Clare Blackburn, who led the research, explains.
“Our results suggest that targeting the same pathway in humans may improve thymus function and therefore boost immunity in elderly patients, or those with a suppressed immune system,” she continues.
“However, before we test this in humans we need to carry out more work to make sure the process can be tightly controlled.”
According to the scientists, the restored thymus was fully functioning and “very similar” to the thymus of a young mouse – in fact, it was twice the size of the thymus in the old control mice.
Although the researchers have not yet ascertained whether the immune systems of the mice with a restored thymus were strengthened by the process, they do know that mice receiving this treatment began to produce more T cells.
The recovery of the organ in the old mice was sustainable, but further research is needed to ensure that there were no unintended adverse effects.
Commenting on the procedure, Dr. Rob Buckle, head of Regenerative Medicine at the MRC, says:
“One of the key goals in regenerative medicine is harnessing the body’s own repair mechanisms and manipulating these in a controlled way to treat disease. This interesting study suggests that organ regeneration in a mammal can be directed by manipulation of a single protein, which is likely to have broad implications for other areas of regenerative biology.”
Other recent developments in regenerative medicine have included a new technique to yield potent, renewable human stem cells, and the creation of a new substance, which could simplify the manufacture of cell therapy.