Stem cell research goes skin deep


Courtesy Theodora Mauro

Theodora Mauro and researchers at King’s College London developed a database of skin cells from stem cells.

By Sports & Health Editor

New skin layers developed from human embryonic stem cells may provide dermatologists and researchers a more efficient way of studying skin diseases.

Theodora Mauro, service chief at the San Francisco Veterans Affairs Medical Center and professor at the University of California, San Francisco, recently developed a system that transforms human embryonic stem cells into skin cells using fibroblasts—cells in connective tissue that produce collagen and other fibers.

In a study published April 24 in the journal Cell Press, Mauro teamed up with Dusko Ilic, senior lecturer at King’s College London to study skin diseases without the use of animal models or skin biopsies. The result was a virtually infinite database of skin cells created from embryonic stem cells.

Mauro, who has been studying skin for 26 years, said she became interested in the skin barrier function because of its important role in keeping water in and bacteria out.

The Chronicle spoke with Mauro about her work with the skin barrier function, the skin cell study and the controversy surrounding stem cell research.

THE CHRONICLE: How did you become interested in this field?

THEODORA MAURO: The problem with the skin barrier is that it’s been really hard to study because it’s been really hard to develop a model for it. What we did first was develop this model with human skin cells—not stem cells. The advantage of that was that they’re a little easier to work with, but the disadvantage of human skin cells is that there’s a lot of variability in them. If you develop these cultures from one person’s skin cells, they often don’t behave the way skin cells from another person do. The other problem with skin cells is that there’s a finite number that you can make and when you want to start doing high-input testing through chemicals, for example, you need a supply that’s bigger than that. So we turned to stem cells and you ended up with pretty nice looking skin.

CC: What inspired the study?

TM: We wanted to establish a good model of skin to be able to look at skin diseases and to also be able to look at the normal functions of normal skin. People have either generally used biopsies of human skin or they’ve used mice in the past. Neither of them are optimum.

CC: What applications might the study’s results have?

TM: We were really trying to address a lot of questions about barrier function, not one specific disease. I think replacing animals and also being able to look at particular skin diseases are probably the two major applications. You’re going to be able to see researchers studying different diseases within the next couple of years.

CC: Are these skin layers similar to natural skin layers?

TM: They have the same functionality that the skin itself would have. They have a good barrier to keeping water from going out and for keeping things from going in. They differentiate fully and they respond to an insult and they repair themselves the same way that skin would. What they don’t do is do functions of the skin that require an immune system. For example, they can’t model an allergic response yet. That’s going to be our next process: to see if we can get that to happen.

CC: Are the layers susceptible to the same diseases as natural skin layers?

TM: One of the nice functions of these skin equivalents [is they tell] you what gene doesn’t work well in a skin disease. For example, if you take atopic dermatitis, which a lot of little kids have right now. We know a lot of the skin diseases are caused by a gene called filaggrin. What we can do is knock that protein out selectively in our cultures. It gives us a lot of flexibility to model diseases without having to take skin biopsies from people who have those diseases. It’s a nice advance. It will really make studying these diseases a lot easier.

CC: Do you think the controversy surrounding stem cell research could hinder further research?

TM: No. Our study used both human embryonic stem cells but also IPS cells, which are cells that are taken from a fibroblast and then turned back into a stem cell and then into a keratinocyte. You don’t have to necessarily use embryonic stem cells to make this preparation.