Leading science, pioneering therapies

Fully functional immune organ grown in mice from lab-created cells

24 August 2014

Scientists have for the first time grown a complex, fully functional organ from scratch in a living animal by transplanting cells that were originally created in a laboratory. The advance could in future aid the development of ‘lab-grown’ replacement organs.

Researchers from the MRC Centre for Regenerative Medicine, at the University of Edinburgh, took cells called fibroblasts from a mouse embryo and converted them directly into a completely unrelated type of cell - specialised thymus cells - using a technique called ‘reprogramming’. When mixed with other thymus cell types and transplanted into mice, these cells formed a replacement organ that had the same structure, complexity and function as a healthy native adult thymus. The reprogrammed cells were also capable of producing T cells - a type of white blood cell important for fighting infection - in the lab.

Fibroblasts transformed into induced thymic epithelial cells (iTEC) in vitro (left, iTEC in green).  iTEC transplanted onto the mouse kidney form an organised and functional mini-thymus (right, kidney cells in pink, thymus cells in dark blue).

The researchers hope that with further refinement their lab-made cells could form the basis of a readily available thymus transplant treatment for people with a weakened immune system. They may also enable the production of patient-matched T cells. The research is published today in the journal Nature Cell Biology.

The thymus, located near the heart, is a vital organ of the immune system. It produces T cells, which guard against disease by scanning the body for malfunctioning cells and infections. When they detect a problem, they mount a coordinated immune response that tries to eliminate harmful cells, such as cancer, or pathogens like bacteria and viruses.

People without a fully functioning thymus can’t make enough T cells and as a result are very vulnerable to infections. This can be a particular problem for some patients who need a bone marrow transplant (for example to treat leukaemia), as a functioning thymus is needed to rebuild the immune system once the transplant has been received. The problem can also affect children; around one in 4,000 babies born each year in the UK have a malfunctioning or completely absent thymus (due to conditions such as DiGeorge syndrome).

Thymus disorders can sometimes be treated with infusions of extra immune cells, or transplantation of a thymus organ soon after birth, but both are limited by a lack of donors and problems matching tissue to the recipient. Being able to create a complete transplantable thymus from cells in a lab would be a huge step forward in treating such conditions. And while several studies have shown it is possible to produce collections of distinct cell types in a dish, such as heart or liver cells, scientists haven’t yet been able to grow a fully intact organ from cells created outside the body.

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

“The ability to grow replacement organs from cells in the lab is one of the ‘holy grails’ in regenerative medicine. But the size and complexity of lab-grown organs has so far been limited. By directly reprogramming cells we’ve managed to produce an artificial cell type that, when transplanted, can form a fully organised and functional organ. This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab.”

The researchers carried out their study using cells (fibroblasts) taken from mouse embryos. By increasing levels of a protein called FOXN1, which guides development of the thymus during normal organ development in the embryo, they were able to directly reprogramme these cells to become a type of thymus cell called thymic epithelial cells. These are the cells that provide the specialist functions of the thymus, enabling it to make T cells.

The induced thymic epithelial cells (or iTEC) were then combined with other thymus cells (to support their development) and grafted onto the kidneys of genetically identical mice. After four weeks, the cells had produced well-formed organs with the same structure as a healthy thymus, with clearly defined regions (known as the cortex and medulla). The iTEC cells were also able to produce different types of T cells from immature blood cells in the lab.

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

“Growing ‘replacement parts’ for damaged tissue could remove the need to transplant whole organs from one person to another, which has many drawbacks – not least a critical lack of donors. This research is an exciting early step towards that goal, and a convincing demonstration of the potential power of direct reprogramming technology, by which once cell type is converted to another. However, much more work will be needed before this process can be reproduced in the lab environment, and in a safe and tightly controlled way suitable for use in humans.”

The study was funded by Leukaemia & Lymphoma Research, Darwin Trust of Edinburgh, the MRC and the European Union Seventh Framework Programme.


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Notes to editors

Publication details.

To request an interview with the authors or for further information please contact the MRC press office on 0207 395 2345 (out of hours: 07818 428 297) or email press.office@headoffice.mrc.ac.uk.

The paper, entitled ‘An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts’, by N Bredenkamp et al, is published in the journal Nature Cell Biology. DOI: 10.1038/ncb3023

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

Leukaemia & Lymphoma Research is a leading UK charity dedicated to improving the lives of patients with all types of blood cancer, including leukaemia, lymphoma and myeloma. Its life-saving work is focused on finding causes, improving diagnosis and treatments, and running groundbreaking clinical trials for all blood cancer patients. The charity champions patients’ needs by influencing relevant policy and decision makers. Its communities give blood cancer patients and their families a place where they can find support and information and share their journey with other people who can relate to what they are going through. Around 38,000 people of all ages, from children to adults, are diagnosed with blood cancers and related disorders every year in the UK. For more information visit info@beatingbloodcancers.org.uk

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