For the first time, researchers have been able to develop a functional thymus by using reprogrammed lab-created cells. The research was led by Clare Blackburn MRC Centre for Regenerative Medicine at the University of Edinburgh and the paper was published in the journal Nature Cell Biology.
The thymus is the organ responsible for the maturation of T cells, which are essential to a functional immune system. Disease and aging can compromise the thymus, though some birth defects like DiGeorge syndrome will fail to fully form the organ at all. While thymus transplants or immune cell infusions can be given for these patients, organ availability and complications with tissue matching do not make it a smooth alternative. Because these problems extend to all donated organs, biologists have been working toward creating custom-made replacement organs using progenitor cells. The advancement from Blackburn’s team makes a significant step forward in the feasibility of that goal.
“The ability to grow replacement organs from cells in the lab is one of the ‘holy grails’ in regenerative medicine,” Blackburn explained in a press release. “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 organized and functional organ. This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab.”
The researchers first obtained fibroblasts, which are cells within connective tissue, from mouse embryos. Next, they used a protein readily found in the thymus during embryonic development called FOXN1 to transform the fibroblasts into induced thymic epithelial cells (iTEC). The cells were then subjected to growth factors and other thymus cells, and were attached to mouse kidneys to grow and mature. After a period of four weeks, the cells had developed into a structure that was just like a thymus that had grown under natural conditions. Surprisingly, these organs were also able to produce T cells, which made them the first functional organ grown from lab-created cells that had been transplanted into an animal.
It will be a while before researchers will be able to replicate this process using human cells, and many more years still before it could be used in clinical practice. However, the success of growing a functional organ within mice leaves scientists hopeful that this could eventually be used to grow a replacement organs for infants with DiGeorge syndrome, who typically do not survive the first year of life without a functional thymus. It could also be used for leukemia patients who have undergone bone marrow transplants and have critically weakened immune systems.