Researchers reveal regenerative potential of the thymus

Thymus

Researchers have identified stem cells in the human thymus for the first time, representing a potential new target to understand immune diseases and cancer.

The thymus is a gland located in the front part of the chest, the place where thymocytes (the cells in the thymus) mature into T cells. The thymus has a unique and complex 3D structure, including an epithelium (a lining of cells able to guide T cell maturation) that forms a mesh throughout the whole organ and around the thymocytes.

As it is relatively inaccessible and shrinks with age – and because its function was discovered only a few decades ago – the thymus has only been investigated for a short period of time compared to other organs. Until now, scientists believed it didn’t contain ‘true’ epithelial stem cells, but only progenitors arising in foetal development.

However, these findings, from the Francis Crick Institute in the UK, show for the first time the presence of self-renewing stem cells, which give rise to the thymic epithelial cells instructing thymocytes to become T cells.

This suggests the thymus plays an important, regenerative role beyond childhood, which could be exploited to boost the immune system.

Roberta Ragazzini, Postdoctoral Research Associate at the Crick and UCL, and first author of the paper, said: “It’s paradoxical that stem cells in the thymus – an organ which reduces in size as we get older – regenerate just as much as those in the skin – an organ which replaces itself every three weeks. The fact that the stem cells give rise to so many different cell types hints at more fundamental functions of the thymus into adulthood.”

Could boost immune response to cancer

The scientists demonstrated that thymic stem cells contribute to the environment by producing proteins of the extracellular matrix, which functions as their own support system.

These stem cells, named Polykeratin cells, express a variety of genes allowing them to give rise to many cell types not previously considered to have a common origin. They can develop into epithelial as well as muscle and neuroendocrine cells, highlighting the importance of the thymus in hormonal regulation.

The researchers demonstrated that all the complex cells in the thymus epithelium could be produced from a single stem cell, highlighting a remarkable and yet untapped regenerative potential.

Paola Bonfanti, Senior Group Leader of the Epithelial Stem Cell Biology and Regenerative Medicine Laboratory at the Crick, said: “This research is a pivotal shift in our understanding of why we have a thymus capable of regeneration. There are so many important implications of stimulating the thymus to produce more T cells, like helping the immune system respond to vaccinations in the elderly or improving the immune response to cancer.”

The researchers will next study thymic stem cell properties throughout life and how to manipulate them for potential therapies.

Edited by Diana Spencer, Senior Digital Content Editor, Drug Discovery World

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