Human T-cells, a vital component of the immune system, have been successfully differentiated from embryonic stem cell (ES cells) for the first time. The work shows that it may be possible in the future to utilise ES cells to help fight diseases affecting the immune system such as human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and X-linked severe combined immunodeficiency (X-SCID), also known as 'bubble boy' disease.
Researchers from the UCLA AIDS Institute and the Institute for Stem Cell Biology and Medicine used a three step process to force the stem cells to change into T-cells. First they inserted a marker gene into the embryonic stem cells, they then grew the cells on a layer of mouse bone marrow cells and finally injected them into a piece of human thymus which was implanted into a mouse with a deficient immune system. Results showed that 24 per cent of the T-cells in the implanted thymus were derived from the stem cells as shown by the incorporated marker. The research is published in the Proceedings of the National Academy of Sciences.
T-cells are an integral part of the body's immune system and, if they are destroyed or inactivated, the body cannot fight infections. In the early stages of AIDS, the HIV virus targets a particular molecule, coded by the gene CCR5, on the surface of T-cells in order to attack and destroy them, thereby damaging the body's immune responses. Based on this research scientists may one day be able to modify undifferentiated stem cells to display an inactivate copy of the CCR5 gene - and repopulate the thymus with cells unable to be attacked by the virus. In a disease such as X-SCID stem cells could be manipulated to obtain functional T-cells and re-implanted. It is not yet known if it will be possible to match stem cells to a patient to prevent compromised immune systems rejecting any implants.
The research is particularly useful as T-cells are difficult to study in conventional ways, researcher on the paper Jerome Zack commented. 'Introducing new genes is inefficient in T-cells and can activate the cells in inappropriate ways', he explained. The thymus is located just above the heart in humans and is the location for the production of T-cells - problems with the thymus can lead to blood diseases and, as it shrinks over time, the immune system gradually weakens with advancing age. The researchers hope that the work will give them clues as to how ES cells are able to differentiate into mature T-cells. 'That way we can eventually repopulate the immune system in patients needing T-cells', said Zack.
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