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.
The technique, so far only tested on mice, could 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 bypassed 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 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.
"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.
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.
Around one in 4,000 babies born each year in the
Thymus disorders can be treated with infusions of extra immune cells or transplantation of a new organ soon after birth. However, such approaches are limited by a lack of donors and tissue rejection. The research, published in the journal Nature Cell Biology, raises the possibility of creating a whole new functioning thymus using cells manufactured in the laboratory.
"This research is an exciting early step towards that goal. However, much more work will be needed before this process can be reproduced in the lab environment, and in a safe and tightly controlled way suitable for use in humans."
Cells transplanted onto a mouse kidney to form a mini-thymus, the first working organ created outside
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