Researchers from the Francis Crick Institute and University College London have rebuilt a human thymus using human stem cells and a bioengineered scaffold. This work is an important step towards the ability to build artificial thymi that could be used as transplants.
The thymus is a primary lymphoid organ. It is where haematopoietic progenitors are instructed to become functional T cells. The epithelial component of the thymus stroma derives from the endoderm. Whereas mesenchymal stroma derives from the neural crest and in part from incoming vessels. The thymus has a fundamental role in immune regulation. It controls the development of both immune competence and tolerance. If the thymus does not work efficiently or does not form fully, several diseases can manifest, such as severe immunodeficiency. As a result, its functional dissection and subsequent reconstruction may provide powerful tools applicable to many medical conditions. For example, thymic therapeutic strategies may be applicable to organ transplantation in which tolerance is a key obstacle to long-term graft acceptance.
Previous attempts to rebuild a fully functional thymus have seen limited success. This is largely been due to the organ’s inherent complexity. In this proof-of-concept study, published in Nature Communications, scientists rebuilt thymi using stem cells. These stem cells were taken from patients who had to have the organ removed during surgery.
Researchers used the donated tissue to grow thymic epithelial and thymic interstitial cells in the laboratory. The team then developed a new microvascular surgical approach to remove all the cells from rat thymi. From this, only the structural scaffolds remained. The researchers then injected the organ scaffolds with up to six million human thymic epithelial cells as well as interstitial cells. They found that the cells grew onto the scaffolds and after only five days, the organs developed to a similar stage as those seen in nine-week old foetuses. Finally, the team implanted these thymi into mice. They observed that in over 75% of cases, the thymi were able to support the development of human lymphocytes.
These findings offer practical prospects for treating congenital and acquired immunological diseases. The team are continuing their work rebuilding thymi to refine and scale up the process. Paola Bonfanti, senior author, stated:
“As well as providing a new source of transplants for people without a working thymus, our work has other potential future applications.
For example, as the thymus helps the immune system to recognise self from non-self, it poses a problem for organ transplants as it can cause the immune system to attack the transplant.
It is possible that we could overcome this by also transplanting a thymus regrown from cells taken from the thymus of the organ donor. We are confident that this may prevent the body attacking the transplant. The research behind this is still in early days, but it is an exciting concept which could remove the need for patients to take immune suppressors for the rest of their life.”
Image credit: By wildpixel – canva.com