Yann Barrandon is a joint professor of Stem Cell Research and of Experimental Surgery at the Swiss Federal Institute of Technology Lausanne (EPFL) and the University of Lausanne (UNIL). He is also Head of the Department of Experimental Surgery at the Lausanne University Hospital (CHUV).
Yann is a long-standing faculty member of the successful European Summer School on Stem Cells & Regenerative Medicine, held annually in Hydra, Greece. At this year’s School we caught up with him about his research, and future directions in stem cell science.
What is your research all about?
My lab is focusing on two complementary projects at the moment. One aims to develop a genetic treatment for an inherited skin disease called epidermolysis bullosa. The other is about stem cell plasticity – can we take a stem cell that is supposed to make one kind of tissue, and use it to make something else?
How do you make a stem cell do something it wouldn’t normally do?
We do it just by manipulating the microenvironment – in other words, the proteins and other molecules or compounds in the immediate surroundings of the cell, plus other aspects of the environment like temperature or pH. The idea is to take an adult stem cell, one we can get from a person at any stage after birth, and manipulate that cell’s behaviour just by playing around with its microenvironment. The trick is to find a source of adult stem cells that we can do this with. For example, we recently published a paper showing that stem cells taken from the thymus of a rat can be made to function as hair follicle stem cells, which are normally found in the skin. We did this just by putting the cells from the thymus into the proper microenvironment for hair follicle stem cells. So it’s a form of reprogramming of the cells, but without any manipulation of the genes in the cells.
Why is it useful to reprogramme cells without genetic modification?
Well, if you can find out what the microenvironment is doing, you may be able to use that knowledge to treat stem cells in the lab so that they make skin, pancreas or liver, without any genetic changes to the initial stem cells. That could be really useful for medicine. I think techniques involving genetic modification are going to be very hard to get through regulatory controls because of concerns about safety. If you want to use the cells on patients, you have to demonstrate safety before you begin to think about testing reproducibility or effectiveness of a treatment. You have to demonstrate that the cells will not cause a disease. Among the diseases people are concerned about is cancer. Some of these safety concerns are removed if you can find a way to control the cells without interfering with their genes.
But you’re also working on a gene therapy…
Yes, we are trying to create a gene therapy for a genetic skin condition called epidermolysis bullosa. This disease causes the skin to blister continuously. In its severe form, it’s a life-threatening problem. Because of the safety concerns surrounding genetic modification of cells, we work on a single cell level. We take a single human skin stem cell and repair the genetic defect. We can select the best cell to use, and then we can demonstrate that the progeny of this cell – the new cells it makes when it divides – do not form tumours. And then we know that we can grow more cells that won’t form tumours in the patient. Of course there are concerns other than cancer. You need to make sure the cells won’t go to the wrong part of the body, or make the wrong kind of tissue when they are put into the patient. So there is a lot to think about.
How close are you to a successful gene therapy for epidermolysis bullosa?
We are in the last stage - the most complicated, but the most exciting one: going to the patient. We hope to be able to do a transplant in a trial patient in a year's time.
"The answers lie during early development... everything in the body is set up during development"
Your research spans basic science and clinical applications. What drives you in your work?
I’m interested in understanding why patients have diseases, and how we can cure these diseases.They’re the main questions that have been driving my research all my life. To answer these questions you might start from a clinical point of view, but you have to get more and more into basic science. That brings up more and more questions. Then you begin to understand that the answers to your questions lie during early development, especially if you work with stem cells. Everything in the body is set up during development.
What big breakthrough would you like to see in stem cell science?
I would say that a big breakthrough would be to find a cell in the normal healthy human being that can be used to produce all the different types of cell in the body. So, a cell that’s equivalent to an induced pluripotent stem cell (iPS cell), but exists naturally in our bodies. These cells may exist or they may not exist at all. But if such a cell does exist, there would be no need for iPS technology.
What is your favourite thing to do after a long day in the lab?
Walk my dog in the countryside. I have also developed enormous competence in taking a siesta!
Find out more
More about Yann Barrandon:
Information for epidermolysis bullosa patients:
- DEBRA International, an alliance of national associations of people living with Epidermolysis Bullosa
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, USA
- Epidermolysis bullosa information from the UK National Health Service
Related articles on EuroStemCell:
Scientific papers on skin stem cell research:
- Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells, Bonfanti et al, Nature 2010; 466(7309):978-82
- Altering cell fate: From thymus epithelium to skin stem cells, Bilousova G and Roop DR, CellStemCell 2010; 7:419-420
- Epidermal homeostasis: A balancing act of stem cells in the skin, Blanpain C, Fuchs E, Nat Rev Mol Cell Biol 2009; 10(3):207-17
- Oligopotent stem cells are distributed throughout the mammalian ocular surface, Majo F, Rochat A, Nicolas M, Jaoudé GA, Barrandon Y, Nature 2008; 456(7219):250-4