25 August 2014

Bioengineers have grown a working thymus from cells

They have grown the most important organ of the immune system, and it works

Nadezhda Markina, Newspaper.RuFor the first time, scientists have grown a full–sized organ that works safely in a living organism: we are talking about the most important element of the immune system - the thymus gland, which the Scots grew and planted mice.

"Newspaper.Ru" tells about which organs have learned to grow in the laboratory today.

It was grown from mouse fibroblast cells, and for this bioengineers did not have to turn them into stem cells, instead they managed to directly reprogram them into thymus cells.

This study, which the authors wrote about in the journal Nature Cell Biology (Bredenkamp et al., An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts), is a very important step towards growing organs for transplantation, although it will take another ten years to apply the technology to humans.

The thymus is the "training base" of the body's immune system. Located in the upper part of the chest, the thymus gland trains the cells of the immune system, T-lymphocytes, to protect the body from the invasion of infection. T-cells are formed in the bone marrow, then they enter the thymus and it is in it that they mature, finally specialize in different types and tune in to their service.

In people with a lack of thymus function, T cells do not cope well with the task of organizing the body's immune response to infection. The role of the thymus is especially important for patients who have undergone bone marrow transplantation, whose immunity is completely suppressed and immune protection needs to be rebuilt after surgery.

Congenital underdevelopment or complete absence of the thymus occurs – this leads to a pathological condition called Di Giorgi syndrome.

If the thymus is absent or does not work at all, the best solution is its transplantation, but, of course, there is a problem of shortage of donor organs. Growing a bioengineered organ for these purposes would help save the lives of such people.

The team of Professor Claire Blackbon from the Center for Regenerative Medicine at the University of Edinburgh used fibroblast cells from a mouse embryo as a starting material. Then the scientists reprogrammed them, changing the work of just one gene. As a result of this manipulation, the level of the FOXN1 protein in the cells increased, the same one that ensures the development of the thymus during the laying of organs in the embryo. Since the FOXN1 protein belongs to transcription factors, it regulates the work of other important genes.

So fibroblasts turned into thymus epithelial cells – this is the most important element of the thymus gland: they work with T cells.

However, these cells alone were not enough, and scientists mixed them with other, supportive, thymus cells. And what happened was planted in a live mouse – in a kidney capsule. Four weeks later, a full-sized thymus grew inside the capsule of a mouse kidney. It did not differ in structure from the natural thymus, it consisted of bark and median substance. Moreover, the bioengineered thymus worked, fulfilling its inherent role.

The grown thymus was tested in action. Tests have confirmed that in the mouse body it produces various types of T cells from immature blood cells - CD4 and CB8 cell populations.

CD4 are helper cells that send signals to control the immune response, and CB8 are killer cells that directly attack and kill infected and cancer cells.

Scientists emphasize that, although specialized cells were obtained in the laboratory by reprogramming cells and fragments of organs (liver, heart, and even brain) were grown before, a full-size working organ has not yet been grown.

For example, as the newspaper wrote.En", scientists from the University of Texas have grown full–sized human lungs, although they have not yet checked whether they will work (for this it is supposed to plant them in pigs); researchers from Stanford received human liver cells – hepatocytes from fat cells - liposuction waste; scientists from San Francisco turned human fibroblasts into cardiomyocytes; Austrian bioengineers received there is a model of a human eye in a Petri dish. Inner ear cells, blood vessels, etc. were also obtained.

However, there are also examples of working bodies. However, scientists used stem cells for this. For example, bioengineers from the University of Texas grew lacrimal and salivary glands that worked in mice. The Japanese from the University of Tokyo grew a fragment of muscle tissue that was shrinking. And other Japanese scientists have grown a working human liver in the body of a mouse. Finally, Anthony Atala got a working miniature kidney.

As for the bioengineered thymus, scientists admit that it will take another ten years to develop a technology that is suitable and completely safe for humans.

"This work is an impressive step forward towards the big goal of growing human organs," said Rob Buckle, head of the Department of regenerative Medicine. – It demonstrates the possibilities of direct cell reprogramming technology, which turns cells of one type into cells of another type. Nevertheless, there is still a lot of work to be done before creating a suitable and safe technology for its use in humans."

Portal "Eternal youth" http://vechnayamolodost.ru25.08.2014

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