Scientists build whole functioning thymus from human cells

Researchers from two leading national organisations have rebuilt a human thymus using human stem cells and a bioengineered scaffold thanks to support from the NIHR GOSH Biomedical Research Centre (BRC). Their work, which has been published in Nature Communications, is an important step towards being able to build artificial thymi which could be used as transplants.

The thymus is an essential organ in the chest where T lymphocytes, which play a vital role in the immune system, mature. If the thymus does not work properly or does not form during foetal development in the womb, it can lead to diseases such as severe immunodeficiency, where the body cannot fight infectious diseases, cancerous cells, or conditions where the immune system mistakenly attacks the patient’s own healthy tissue.

In their proof-of-concept study, the scientists from the Francis Crick Institute (Crick) and University College London (UCL) rebuilt thymi using stem cells donated by patients from Great Ormond Street Hospital (GOSH) who had to have the organ removed during surgery. When transplanted into mice, the bioengineered thymi were able to support the development of mature and functional human T lymphocytes.

While researchers have previously rebuilt other organs or sections of organs, this is the first-time scientists have successfully rebuilt a whole working human thymus. The study, which was also funded in large part by the European Research Council (ERC), is an important step not only for further research into and treatment of severe immune deficiencies but also more broadly for developing new techniques to grow artificial organs.

Paola Bonfanti, whose thymus work is funded in part by the BRC, is senior author and group leader at the Crick and said: “As well as providing a new source of transplants for children born without a working thymus, our work has other potential future applications. For example, this work may impact the future of organ transplantation.

“The thymus helps the immune system recognise foreign cells and tissues, which poses a problem for organ transplants as it can cause the immune system to attack the new organ. It’s possible that we could overcome this problem by also transplanting a thymus regrown from cells taken from the thymus of the organ donor, which we think may prevent the body attacking the transplant.

The UCL professor also added:

To rebuild this organ, researchers collected the donated thymi from patients undergoing cardiothoracic surgery at GOSH. In the lab, they then grew thymic epithelial cells and thymic interstitial cells into many colonies of billions of cells.

Using a microvascular surgical technique newly developed by the team, researchers obtained a structural scaffold from rat thymi to use as a base for the cultured thymic cells to grow on. The scaffolds were then injected with up to six million human thymic epithelial cells as well as interstitial cells from the colonies grown in the lab. After only five days, the cells not only grew onto the scaffolds, but the organs had developed to a similar stage as those seen in nine-week old foetuses.

As a final step, the team implanted these thymi into mice where they found that in over 75% of cases, the organs were able to support the development of human lymphocytes.

The ability to expand thymic stem cells taken from human donors into large colonies is a promising prospect that the researchers will look to scale up the process with a view to build ‘human size’ thymi”. GOSH is the only centre in Europe and one of two worldwide where children born without a thymus are transplanted with donor thymi. The hope is to one day see this safely translated into clinical practise in the very near future.