Scientists regenerate immune organ in mice

Scientists have for the first time used regenerative medicine to fully restore a degenerated organ in a living animal, a discovery that could pave the way for future human therapies.

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The team from the Medical Research Council (MRC) Centre for Regenerative Medicine, at the University of Edinburgh, rebuilt the thymus of very old mice by reactivating a natural mechanism that gets shut down with age.

The regenerated thymus was very similar to one in a young mouse in terms of structure and the genes expressed. The function of the organ was also restored, and mice receiving the treatment began making more T cells – a type of white blood cell important in fighting infection. However, the researchers do not yet know if the immune system of the older mice was strengthened. The research is published today in the journal Development.

Prof Clare Blackburn from the MRC Centre for Regenerative Medicine, at the University of Edinburgh, who led the research, said:

“By targeting a single protein, we have been able to almost completely reverse age-related shrinking of the thymus. 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. However, before we test this in humans we need to carry out more work to make sure the process can be tightly controlled.”

The thymus, located in front of the heart, is the first organ to deteriorate as we age. This shrinking is one of the main reasons our immune system becomes less effective and we lose the ability to fight off new infections, such as flu, as we get older.

Researchers targeted a key part of this process – a protein called FOXN1, which helps to control how important genes in the thymus are switched on. They used genetically modified mice to enable them to increase levels of this protein using chemical signals. By doing so they managed to instruct immature cells in the thymus – similar to stem cells – to rebuild the organ in the older mice. The regenerated thymus was more than twice the size than in the untreated mice.

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, said:

“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.”

Previous attempts to provoke thymus regeneration have involved using sex hormones, but these have resulted in only temporary recovery of size and function of the organ. In this study, the recovery of the thymus was sustainable, but more work is needed to ensure there are no unintended consequences of increasing FOXN1.

The research was funded by Leukaemia and Lymphoma Research, the Darwin Trust of Edinburgh, the MRC and the European Union.

Notes to editors

Publication details.

1. The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. www.mrc.ac.uk 
2. The MRC Centre for Regenerative Medicine (CRM) is a world leading research centre based at the University of Edinburgh. Scientists and clinicians at CRM study stem cells, disease and tissue repair to advance human health. The Centre is based at the Scottish Centre for Regenerative Medicine (SCRM) building, on a site shared by the Royal Infirmary Hospital and the University's Clinical Research facilities. With new state-of-the-art facilities and a 230+ team of scientists and clinicians, CRM is positioned uniquely to translate scientific knowledge to industry and the clinic. www.crm.ed.ac.uk
3. Prof Clare Blackburn is also coordinator of ThymiStem, a newly-established international consortium, funded by the EU, which aims to develop new thymus-based strategies for improving immune system function in patients. www.thymistem.org