For the first time, researchers have grown a complex and fully functional organ inside a live animal from cells created outside the body. More research is needed before the technique can be applied to people, but the advance brings us one step closer to lab-grown organs.
“The ability to grow replacement organs from cells in the lab is one of the ‘holy grails’ in regenerative medicine,” said study author Clare Blackburn, a professor of tissue stem cell biology at the MRC Centre for Regenerative Medicine at the University of Edinburgh, in a press release. “But the size and complexity of lab-grown organs has so far been limited.”
The technique was described online August 24 in the journal Nature Cell Biology. Researchers reprogrammed connective tissue cells, known as fibroblasts, to look and act like cells from the thymus. The thymus is an organ located just under the breastbone and above the heart and is part of the immune system. It is responsible for producing the T-cells needed to fight infections in the body that are caused by bacteria and viruses.
In addition to helping children born without a thymus, artificial organs could boost the immune systems of bone marrow transplant patients after their treatment. The organs could also benefit older adults. As people age, their thymus shrinks, leaving them with a reduced ability to fight new infections.
Thymus Cells Reprogrammed from Connective Tissue Cells
The researchers first reprogrammed fibroblasts from a mouse embryo. The reprogrammed fibroblasts expressed a gene that is not usually active in these types of cells. As a result, the cells changed their shape to more closely resemble thymus cells. They also began to express other thymus-specific genes. Researchers showed that in the lab these cells supported the production of T-cells, an essential part of creating a functioning thymus.
“By directly reprogramming cells, we've managed to produce an artificial cell type that, when transplanted, can form a fully organized and functional organ,” said Blackburn. “This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab.”
In the next stage of the process, researchers transplanted these reprogrammed cells, along with other types of thymus cells, onto the kidneys of mice. After four weeks, the cells grew to form a replacement organ with the same structure and function as a native thymus. Blood tests revealed that by eight weeks, the newly-grown thymuses were producing T-cells in some of the mice.
One Approach to Lab-Grown Organs
This work is just one approach to growing organs that scientists are testing, but it does offer certain advantages. Making thymus cells from fibroblasts taken from the same animal reduces the chance that the organ will be rejected. Current donation programs in people require that the organs be closely matched between the donor and recipient to avoid the organ being rejected by the recipient’s immune system.
Before researchers can attempt to grow a thymus in people, however, the work will need to be replicated using human cells and other animals. If successful, this technique could alleviate some of the demand for organs, at least in the case of the thymus.
“Growing ‘replacement parts’ for damaged tissue could remove the need to transplant whole organs from one person to another,” Dr. Rob Buckle, head of Regenerative Medicine at the MRC Centre, said in the press release, adding, “which has many drawbacks — not least a critical lack of donors."
Buckle concluded that more work will be needed before this process can be reproduced in the lab environment, and in a safe and tightly controlled way that is suitable for use in humans.