New Medical Research Council (MRC) Centre for Regenerative Medicine research published points to the possibility of direct reprogramming of one stem cell type to another without the need for genetic modification and raises prospects for regenerating organs.
The study shows that stem cells from the thymus, a specialized organ of the immune system, can function as hair follicle stem cells and contribute to the long-term maintenance of the skin, a completely different organ.
In this study, a group of cells called thymic epithelial cells (TECs) were isolated from the rat, cultured in the lab under conditions used to grow skin stem cells, and tested for function and for genetic markers of thymus and skin cell types. They were then transplanted into developing skin.
On transplantation, the cells displayed different genetic markers – those of hair follicle stem cells. They were also able to contribute to maintenance of both skin and hair for more than a year - outperforming bona fide hair follicle stem cells, which can only renew the skin for 3 weeks or after injury.
These experiments show that cues from the local microenvironment – in this case skin - can ‘reprogramme’ stem cells to contribute to tissues they are not normally able to generate. They also raise new questions about relationships between stem cells from different tissues within the body.
"These cells change because of the environment they come into contact with, the skin" comments Professor Yann Barrandon, Joint Chair of Stem Cell Dynamics EPFL/CHUV-UNIL, who led the study. "In theory this operation could be recreated with other organs as well."
When the body plan of an animal is formed, embryos develop into three cellular (germ) layers - ectoderm, endoderm, and mesoderm – and from these layers into the organs and tissues of the body. Ectoderm becomes skin and some nerves, endoderm becomes the gut and organs such as the liver, pancreas and thymus, and mesoderm becomes muscle and blood. Before now we believed that germ layer boundaries could not be crossed – that cells originating in one germ layer could not develop into cells associated with one of the others.
This new research shows that cells from the thymus (endoderm origin) can turn into skin stem cells (ectoderm origin) and suggests germ layer boundaries are less absolute than previously thought.
Dr. Clare Blackburn, thymus specialist at the University of Edinburgh's MRC Centre for Regenerative Medicine and an author on this paper, comments, “It’s not just that a latent capacity is triggered or uncovered when these stem cells come into contact with skin. They really change track – expressing different genes and becoming more potent. It will be interesting to see whether microenvironments other than skin have a similar effect.”
Illustration: This cross-section of skin shows rat thymic epithelial cells (green) contributing to hair follicles and sebaceous glands. –EPFL.
The University of Edinburgh News Release (08/19/10)
Science Daily (08/19/10)
Medical News Today (08/19/10)
Abstract (Nature; 466, 978-982 (08/19/10))