A new study published this week in Developmental Cell has identified the presence of stem cells in the human thymus for the first time. These findings have promising implications for treating autoimmune diseases and cancer, as well as improving immune system function.
Rethinking Stem Cells
Stem cells (SCs) have extensive medicinal applications that are facilitated by their unique ability to develop into different cell types and to self-renew. Growing SCs in vitro presents a more ethical and economic approach to widespread SC therapy. However, currently only epithelial stem cell types can be extensively expanded in this way.
The thymus is a specialised organ with a unique and complex epithelial structure, located behind the sternum and between the lungs. It is involved in the maturation of T cells formed in the bone marrow, hence playing a significant role in the body’s immune response. Throughout postnatal life, the thymus undergoes progressive atrophy. This has dampened research interest in the organ in previous years and led to the belief that it does not contain ‘true’ epithelial SCs. However, new findings suggest that the thymus does contain epithelial SCs and plays a key regenerative role beyond childhood.
From Concealed to Revealed
Researchers from the Francis Crick Institute identified two SC niches (clusters) in the postnatal cortex and medulla of the thymus containing pleiotropic multipotent epithelial stem cells. The thymic epithelial SCs displayed distinct transcriptional profiles and phenotypic traits, including the ability to give rise to various cell types, expanding their regenerative capabilities beyond what was originally thought. Furthermore, the researchers demonstrated that thymic SCs self-renew and self-organise in vitro over extended periods – a fundamental trait of stem cells. These findings have significant implications for addressing a variety of medical problems.
“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,” commented Roberta Ragazzini, first author of the study.
Figure 1 | Visualisation of the different cell types that can develop from thymic epithelial stem cells (Polykeratin cells). Adapted from Ragazzini et al., 2023.
Pluripotent Potential
This study’s findings present the potential to regenerate the thymus from Polykeratin cells. This has a wide range of applications, including transplantation in athymic patients, improving immune function in the elderly, treating individuals with autoimmune diseases, boosting vaccine response in the immunocompromised and amplifying the immune response against cancer.
The authors are now investigating how to stimulate the development of Polykeratin cells into specific cell types through genetic manipulation without compromising their self-renewal capacity.
