Reprogrammed cells created in a laboratory have been used to build a complete and functional organ in a living animal for the first time.
British scientists produced a working thymus, a vital immune system ‘nerve centre’ located near the heart.
In future the technique, so far only tested on mice, could be used to provide replacement organs for people with weakened immune systems, scientists believe. But it might be another 10 years before such a treatment is shown to be effective and safe enough for human patients.
The research by-passed the usual step of generating ‘blank slate’ stem cells from which chosen cell types are derived.
Instead, connective tissue cells from a mouse embryo were converted directly into a completely different cell strain by flipping a genetic “switch” in their DNA.
The resulting thymic epithelial cells (TECs) were mixed with other thymus cell types and transplanted into mice, where they spontaneously organised themselves and grew into a whole structured organ.
The ability to grow replacement organs from cells in the lab is one of the ‘holy grails’ in regenerative medicine
Professor Clare Blackburn, from the Medical Research Council (MRC) Centre for Regenerative Medicine at the University of Edinburgh, who led the team of scientists, said: “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.
“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.”
If the immune system can be compared with an army, the thymus acts as its operations base. Here, T-cells made in the bone marrow are primed to attack foreign invaders, just as soldiers are armed and briefed before going into battle.
Once deployed by the thymus, the T-cells protect the body by scanning for infectious invaders such as bacteria and viruses, or dangerous malfunctioning cells, for instance from tumours. When an “enemy” is detected, the T-cells mount a co-ordinated immune response that aims to eliminate it.
People with a defective thymus lack functioning T-cells and are highly vulnerable to infections. This is especially hazardous for bone marrow transplant patients, who need a working thymus to rebuild their immune systems after surgery.
Thymus disorders can be treated with infusions of extra immune cells or transplantation of a new organ soon after birth.
However, such approaches are severely limited by a lack of donors and tissue rejection.
The new research, published in the journal Nature Cell Biology, raises the possibility of creating a whole new functioning thymus using cells manufactured in the laboratory. While fragments of organs, including hearts, livers and even brains, have been grown from stem cells, no one before has succeeded in producing a fully intact organ from cells created outside the body.