A Hair Closer To Lab-Grown (Mouse) Skin
Advances in stem cells have made it possible to grow and transfer nascent skin tissue to animals. However, researchers still can’t grow functional skin, with hair follicles and sweat glands, to completion yet.
But new research published in Cell Reports this week describes the work of an Indiana University team that’s successfully grown mouse skin complete with hair follicles in the lab. It’s a development that surprised even them—the team was originally working on growing inner ear tissue, not skin.
Karl Koehler, an assistant professor of otolaryngology and head and neck surgery, explains his team’s work, and what makes skin such a complicated organ to synthesize.
Karl Koehler is an assistant professor of Otolaryngology at the Indiana University School of Medicine in Indianapolis, Indiana.
IRA FLATOW: This is Science Friday. I’m Ira Flatow. If you caught our last hour, you know we have Frankenstein on the brain with our sci-fi book club. And what better way to update that monster story where body parts are stolen from graves than to discuss one from this century where body parts are being grown in the labs from stem cells– specifically, skin. Our next story involves an attempt to grow skin in the laboratory, which is a lot more complicated than you might think.
Skin represents a challenge because, even though you can’t see them, skin has dozens of types of cells. And past attempts to grow skin in the lab have yielded a fairly dumbed-down version. But researchers from Indiana University have made new progress in that direction. They have grown mouse skin complete with dermis, epidermis, and hair follicles. Hm, maybe a future answer to baldness.
Well, here to tell us more is Dr. Carl Kohler, Assistant Professor of Otolaryngology and Head and Neck Surgery at Indiana University School of Medicine. He’s a co-author on the new research published this week in Cell Reports. Welcome to Science Friday.
CARL KOHLER: Hi, Ira. Thanks for having me.
IRA FLATOW: Tell us about otolaryngology. What– that’s not a field, right? I tend to associate that with skin cultures?
CARL KOHLER: Yeah, so otolaryngology is– you typically think of ear, nose, and throat. Yeah, so–
IRA FLATOW: How did you get into this?
CARL KOHLER: I’m kind of surprised just like you are. I’m working on skin now. So this work came out of a project where we are trying to actually develop a way of generating the inner ear from stem cells. What we know about how the inner ear develops is that it actually develops from the same sheet of cells that the skin does. So it wasn’t very surprising to us that we were able to generate skin as kind of a byproduct of generating inner ear tissue. However, we were kind of surprised to see both layers of the skin developing, like you mentioned in the intro there. And those cell layers interacted in such a way that allowed hair follicles to develop. It was a bit of a shock to see that in the lab.
IRA FLATOW: So you got hairy skin you didn’t expect.
CARL KOHLER: Yes.
IRA FLATOW: How many layers does skin have?
CARL KOHLER: So there are two basic layers, the epidermis and the dermis. But within each one of those layers, they’re stratified. So you see about three to four different cell types within– kind of specialized cell types– within those layers.
IRA FLATOW: So you get the hair follicles which is very important to skin. Did you expect the hair to come out?
CARL KOHLER: No, no. It was unexpected.
IRA FLATOW: And what about sweat glands? Did you get sweat glands on this too?
CARL KOHLER: So that is something we haven’t seen yet. And it’s not that surprising because sweat glands– these are mouse hairs, remember. And mice only have sweat glands in very specific locations like their feet.
IRA FLATOW: Oh, there’s a little fact for tonight.
CARL KOHLER: Exactly. Unlike humans which have sweat glands all over their body.
IRA FLATOW: So what does this look like? I’m picturing a thin sheet all stretched out in a Petri dish.
CARL KOHLER: Yeah, not quite. That’s kind of one of the revelations from this study is that the way we’re generating the cells, we’re generating the epidermis and the dermis together. And so they develop simultaneously in a three-dimensional environment. So they take on the shape of a cyst or like a ball of cells. And a unique way it’s structured is that the inside of the cyst is actually representative of the outside of the skin, the epidermis. And the outside of the cyst is representative of the dermis. So when the hair follicles develop, the roots are kind of growing outward in all directions, kind of like the petals on a flower. And the hair shafts are growing into the inside of the organoids.
IRA FLATOW: So you’ve got like a hairy ball–
CARL KOHLER: Yes.
IRA FLATOW: –facing inwards. So sort of inside-out, hairy ball.
CARL KOHLER: Yeah, we’ve tried to avoid that terminology because– but that’s essentially what we’re generating. Yeah.
IRA FLATOW: It doesn’t sound very enticing.
CARL KOHLER: Exactly.
IRA FLATOW: So what makes skins so complicated? It seems like such a simple thing when you look at it.
CARL KOHLER: Yeah, so I think it’s underappreciated in its complexity because it does have these two basic layers. But it’s also embedded with these appendages which– in and of themselves there are seven to eight different layers of specialized cells within one hair follicle. And they all have a special function within the developing hair follicle.
And the hair follicle goes through a regenerative cycle over time, over our lifespan, constantly degenerating and then regenerating itself. And there are resident stem cells within the hair follicles that are governing this process. So it is very complicated. And then you’ve got to think about how there’s interactions between the blood vessels and the immune system. And there are a number of nerve endings within the skin that up that complexity.
IRA FLATOW: So what happened? You start out trying to generate inner ear tissue and you wind up with skin.
CARL KOHLER: Yes.
IRA FLATOW: What happened?
CARL KOHLER: So at first, we were seeing the skin generated with the inner ear tissue. And then we tried to kind of create the right environment so that we would just generate the skin tissue. Because that might be more advantageous for doing things like drug screening or modeling skin disorders if you can just generate the skin tissue and the complex cells that interact within the skin.
IRA FLATOW: So why did you get more complex skin out of it than other past attempts?
CARL KOHLER: That’s what we’re actively trying to figure out right now. We think it has something to do with the way that the cells develop together versus past attempts where people have tried to take the individual components of the skin and kind of smash them together in a dish. And that approach has never really lead to the complexity or the cellular diversity that we see in normal skin and certainly hasn’t produced hair follicles in a culture setting.
IRA FLATOW: Last year we heard about the story of a boy who had 80% of his skin on his body replaced. It was grown to an early developmental stage, and then it was grafted to finish developing on his body. If we can do that, what’s the use of skin grown start-to-finish in a lab if it might be easier to do it the other way.
CARL KOHLER: Yeah, that’s a valid point. So that was an amazing study. A very, very exciting breakthrough. One thing that I could think about that we might be able to weave in with our study is that I’m not sure if that technique leads to full regeneration of the skin or just kind of a surface layer of the skin. So we might be able to take our approach and come up with a way of incorporating skin appendages like hair follicles and sweat glands.
IRA FLATOW: But you have hairy little ball. It’s not going to work on somebody’s arm or leg or something. Can you do something about that?
CARL KOHLER: Yeah yeah. So kind of the two main avenues of research that we’re trying to attack right now is figuring out how to use this mouse skin in a dish model as kind of a blueprint or a template for being able to generate hairy skin from human stem cells. And then, on top of that, trying to figure out how to go from this cystic formation and form a more normal-looking layer of skin in a dish and in transplantation studies where we’re transplanting the tissue onto a mouse.
IRA FLATOW: Well, if you can figure out the human baldness problem, you’re going to be a gazillionaire. You know, I’m sure somebody has been thinking about that.
CARL KOHLER: It’s been mentioned. But I think the main focus right now is trying to figure out and use this to study the developmental biology of the skin and understand how hair follicles develop to begin with.
IRA FLATOW: Well, because that’s– that you’re bringing up– that’s a very interesting point because why do we have hair on some parts of us? And we have no hair on our palms of our hands and things like that. What causes it? Is there some sort of clue or cue that says to the DNA, here’s a spot, make hair.
CARL KOHLER: Yeah. One thing we know is that if we look at the genes that are expressed in the dermal cells on different parts of the body, they seem to have a different signature. And we think that the dermal cells are actually instructing what type of skin you generate. And so an interesting aspect of this study is that since we’re kind of slightly tweaking a method for generating inner ear tissue, we are thinking that the skin that’s generated is probably similar to the skin that you see on the outer ear or near where the ear develops. And so think about future applications. Being able to generate site-specific skin might be an interesting thing to look at in the future.
IRA FLATOW: And so what would be your next thing? If you’re going to take this research further and you had a blank check– I’ll give you my blank check question– what would you need? What would you like to do?
CARL KOHLER: Well, I think I’ve already mentioned it. We really are trying to figure out how to take human stem cells and generate these skin organoids.
IRA FLATOW: You don’t want to grow skin on somebody’s inner ear– hair on someone’s inner ear, do you?
CARL KOHLER: That might not be the best application. But it could be useful for reconstructing somebody’s outer ear.
IRA FLATOW: Oh, tell us about that. What do you mean?
CARL KOHLER: So there are certain congenital disorders that lead to malformation of the outer ear. And so you’ve probably seen pictures of the mouse with the human-like ear growing on its back. 3D printed a scaffold that looks like the outer ear. But if that’s going to become standard practice in the clinic, we’re going to have to find ways to not only put cartilage cells on that scaffold but also skin tissue to cover it.
IRA FLATOW: And then how much work– I mean, what do you have to tweak to get the full compliment, to get the sweat glands on to yours?
CARL KOHLER: So there’s actually been some recent research on this showing that during development, hair follicles and sweat glands kind of start out as the same outgrowth of the epidermis. And different signaling mechanisms kind of determine one versus the other. So it might be interesting to take our model and look at that sort of interaction.
IRA FLATOW: Very interesting and quite fascinating, Dr. Kohler. Thank you for taking time to be with us today.
CARL KOHLER: Thank you for having me.
IRA FLATOW: Carl Kohler, Assistant Professor of Otolaryngology and Head and Neck Surgery at Indiana University School of Medicine.