Researchers from the MRC Centre for Regenerative Medicine in Edinburgh, UK, have for the first time produced complete working organs from genetically 'reprogrammed' cells. Engineered cells were inserted into adult mice, where they grew into what appeared to be functional thymuses.
Most cells in a normal thymus rely on the production of a protein called Foxn1 in order to develop correctly. By adding a gene that makes this protein to the cells, the researchers were able to force them to change in both appearance and function to resemble thymus cells. Mixed with other cells and injected into mice, these reprogrammed cells grew into functional, thymus-like organs.
The thymus is a small organ found near the heart that is responsible for developing T-cells, a kind of white blood cell that is crucial for providing immunity to viruses and bacteria. Certain genetic conditions (such as Di George syndrome) and immunosuppressive medical treatments can result in an ineffective thymus, making people susceptible to infection. Being able to regenerate or replace a thymus would enable doctors to provide a working immune system to patients suffering from a number of different conditions.
Due to its relative simplicity, the thymus is an ideal candidate for organ engineering. While other research groups have tried to use similar techniques to generate thymus cells, this paper claims to be the first to be successful in being able to demonstrate all thymic functions.
'By directly reprogramming cells we've managed to produce an artificial cell type that, when transplanted, can form a fully organised and functional organ', said Professor Clare Blackburn, lead author on the paper, which was published in Nature Cell Biology. 'This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab'.
While technologically impressive, the procedure is currently not suitable for use in people. It currently involves using cells derived from fetuses, but the procedure may one day involve cells taken from the patient requiring the transplant, minimising ethical concerns and risks of rejecting foreign tissue.
As Professor Chris Mason from University College London puts it, 'the time and resources required to turn this mouse proof of concept study into a safe and effective routine therapy for patients will be very significant — ten years and tens of millions of pounds at a bare minimum'.