05:20am Thursday 24 August 2017

Scientists discover thymus stem cells

Sphere forming cells in the thymus give rise to both  cortical (red) and medullary (green) thymic epithelial cells.

enlarged view Sphere forming cells in the thymus give rise to both cortical (red) and medullary (green) thymic epithelial cells. | © Sonja Mach, DKFZ

Most people do not even know that it exists: the thymus gland, a small organ that lies behind the breast bone. Without it, however, the body could not mount an immune response and would be defenseless against viruses and bacteria, as can be observed in cases of thymus defects.

Cells of the immune system called T cells migrate from the bone marrow into the thymus where they “learn” to discriminate between “non-self” (is attacked) and “self” (is tolerated). Several years ago, Professor Dr. Bruno Kyewski of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) showed that a multitude of tissue-specific proteins of the body are formed for this purpose in the thymus gland. These proteins serve as demonstration material for the immature immune cells to learn self-tolerance. 

In a process that comprises several stages of maturation and selection, progenitor T cells first pass the cortex and then the medulla of the thymus. These two areas are formed by two distinct lines of thymic epithelial cells (TECs), namely the cortical (cTECs) and the medullary thymic epithelial cells (mTECs).

At the German Cancer Research Center, Ahmet and Olga Ucar and colleagues from the groups headed by Bruno Kyewski and Thomas Hofmann have now been able to prove that both cell types stem from a common progenitor. In the thymus of adult mice, the scientists discovered a rare cell type that exhibits typical properties of stem cells. They used a detection method that is based on the capacity of particular tissue-specific stem cells to form globular structures called spheres, in this case thymus spheres, in the culture dish. The sphere-forming cells divide very slowly, giving rise to a new stem cell (self-renewal) and a progenitor cell of the epithelial thymic cells, which can subsequently go on to develop into mature cTECs and mTECs.
Surprisingly, the thymus stem cells lack a transcription factor called Foxn1 that is considered to be vital for normal thymic epithelial development. Apparently, this transcription factor is not needed until later stages in the development of the TECs.
In the adult human thymus, the researchers in Kyewski’s group also identified a rare cell type that can grow into thymus spheres and which they therefore regard as a stem cell candidate. They now plan to characterize and nourish the potential thymus stem cells. The scientists see a chance for developing a cell therapy using TEC stem cells to correct congenital or acquired thymus defects for treating immune deficiencies or autoimmune diseases.

Ahmet Ucar, Olga Ucar, Paula Klug, Sonja Matt, Fabian Brunk, Thomas G. Hofmann and Bruno Kyewski: The adult thymus contains FoxN1- epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages. Immunity 2014, DOI: 10.1016/j.immuni.2014.07.005

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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