Regenerative Medicine Makes Old Immune Organ Young Again
By Chuck Seegert, Ph.D.
The desire to culture replacement organs for damaged or diseased ones has been a significant driving force since regenerative medicine’s infancy. Now, for the first time, University of Edinburgh researchers have regrown a thymus in a living host by transplanting laboratory-grown cells — fully restoring the function of the organ.
"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,” said Clare Blackburn, professor from the Medical Research Council’s Centre for Regenerative Medicine at the University of Edinburgh and lead researcher of the study, in a recent press release. “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."
Usually located near the heart, the thymus gland is responsible for creating T cells, an important class of white blood cells. These cells guard the body against certain infections and mediate the immune response to eliminate foreign agents in the body.
From viruses to bacteria, the Thymus, through the T cells it creates, plays an important protective role. In fact, people with limited function of this organ have compromised immune function and are predisposed to certain infections. While this condition may be treated using a transplant, there are few donors, and matching tissues is often difficult.
To generate the complex and fully functioning thymus tissue, the team started with fibroblasts, a cell type that is usually unrelated to the specialized cells found in native thymus tissue. According to the press release, “reprogramming” fibroblasts was achieved by increasing levels of a protein called FOXN1, which induces cells to develop into thymic cells during normal embryonic development. In particular, the fibroblasts were led to take on the thymic epithelial cell (TEC) phenotype, which is the cell type that enables the organ to make T cells.
The team described the specifics of their method in an article recently published in the journal Development. In culture, the reprogrammed TECs produced CD4+ and CD8+ T cells. When implanted into mice, these cells produced well-defined organs with a similar structure to that seen in the native tissue. This organ was shown to exhibit all TEC subtypes needed to create T cells and repopulate the animal’s immune system.
To ascertain the effectiveness of the new thymus tissue, only very old mice were used. With age, the thymic gland degenerates, eventually leading to decreased T cell production. While this approach was shown to increase T cell production in the test group, it was not determined that it was increasing the strength of the immune system. That work is yet to be done.
This advance was made possible by allowing the cells to spontaneously organize where they were transplanted in vivo. Another approach that is gaining momentum and may help in the arena of tissue engineering is the 3D printing of cells.
Image Credit: Medical Research Council Centre for Regenerative Medicine