RONALDO SCHEMIDT/AFP/Getty Images
October 30, 2017
Healing skin and regrowing limbs: The science of regeneration
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We all know what happens when you get a cut or scrape. You get a scab, you try not to pick at it, and then after a little while it heals. But what’s really going on under that scab? What superpowers does our skin have to repair itself? And what about other animals like salamanders that can do some pretty extreme healing? We’re going under the skin for this one.
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SPEAKER 1: You're listening to Brains On, where we're serious about being curious.
SPEAKER 2: Brains On is supported, in part, by a grant from the National Science Foundation.
[MUSIC PLAYING]
MOLLY BLOOM: We all get cuts and scrapes.
MATTISON: And we all know what happens.
MOLLY BLOOM: You get a scab-- try not to pick at it-- then after a little while, the cut heals.
MATTISON: Sometimes, you're left with a cool-looking scar.
MOLLY BLOOM: But what's really going on when you heal?
MATTISON: What superpowers does your skin have?
MOLLY BLOOM: And what about other animals--
MATTISON: Like salamanders.
MOLLY BLOOM: --that can do some pretty extreme healing.
MATTISON: We're going under the skin for this one, so keep listening.
MOLLY BLOOM: You're listening to Brains On from American Public Media. I'm Molly Bloom, and here with me today is 12-year-old Mattison. From St. Paul.
MATTISON: Hi, Molly.
MOLLY BLOOM: Now, Matty, you are interested in finding out more about healing, and you even hope to help with that for a job one day. Is that right?
MATTISON: Yeah, so I want to be a surgeon.
MOLLY BLOOM: Very cool. What specific kind of surgeon?
MATTISON: Yeah, like a sports medical orthopedic surgeon.
MOLLY BLOOM: Wow. And what got you interested in that job?
MATTISON: Well, I've always been interested in medicine and medical stuff as a kid because my mom's a nurse, so she's led me into that background.
MOLLY BLOOM: Very cool. So I'm guessing you don't get grossed out very easily.
MATTISON: No.
MOLLY BLOOM: That's good.
MATTISON: Yeah.
MOLLY BLOOM: Well, today, we're going to learn about the process that your future patients and pretty much everyone else, for that matter, goes through when they heal.
MATTISON: We're starting with the question that was sent to us from Leo in Saint Paul, Minnesota.
LEO: When a person gets hurt, how does the skin grow back?
MOLLY BLOOM: We talked to Valerie Horsley to find out.
MATTISON: She's a scientist at Yale University, who studies skin development and regeneration after injury.
MOLLY BLOOM: After you get a cut, the healing process starts right away.
VALERIE HORSLEY: Really, your skin wants to make a barrier, like a Saran wrap over your body. And if there's some hole in that Saran wrap, then your body really wants to repair that hole.
MOLLY BLOOM: When you first get a cut, there are a few things that happen right away.
MATTISON: Your blood vessels constrict, helping to stop the blood flow.
MOLLY BLOOM: Then special cells in your blood, called platelets, rushed to the scene to form a clot.
PLATELET: Here we come. Don't worry, we'll stick together.
MOLLY BLOOM: These platelets start secreting proteins that send messages to different cells.
MATTISON: First, these proteins join up with fibrin.
MOLLY BLOOM: It's a thread-like protein. Imagine little strings in your blood.
FIBRIN: Have no fears, guys. Team fibrin is here. We'll help you finish this clot.
PLATELET: All right, the, gang's all here.
MATTISON: The platelets and the thread-like fibrin join together to form a mesh of material that becomes a scab.
PLATELET: You go there.
FIBRIN: And I'll go over there.
PLATELET: It looks like it's holding.
FIBRIN: Go, us.
VALERIE HORSLEY: Your skin is there to protect your body from the outside environment, keeps bacteria out, viruses out. So the scab is there to protect you from your outside environment. And it's there, really, to just seal over the area like a Band-Aid while everything else is repairing underneath it.
MOLLY BLOOM: There's a lot going on under that scab to repair your skin.
MATTISON: White blood cells come to destroy any germs that may have snuck in the open wound.
WHITE BLOOD CELLS: Bacteria, be gone.
MATTISON: Meanwhile, your platelets send out another signal.
MOLLY BLOOM: This one goes to cells in the skin, called keratinocytes.
FIBRIN: Hey, keratinocytes, we need you over here.
MOLLY BLOOM: Those cells, which make up the top layer of your skin--
MATTISON: Called epidermis.
MOLLY BLOOM: --start migrating to the wound.
KERATINOCYTES: We're coming. Just a sec.
MATTISON: Another signal tell cells in the bottom layer of skin--
MOLLY BLOOM: Called the dermis.
MATTISON: --to migrate over as well.
DERMIS: Fibroblasts, do your thing. We need you over here.
FRIBROBLAST: We hear you. On our way.
MATTISON: These fibroblasts make up the support network under the top layer of skin.
MOLLY BLOOM: It's really an all hands on deck situation. All the cells nearby that can help are called into service.
VALERIE HORSLEY: So we know that there are stem cells in the hair follicles. And normally, they don't go up into the top layer of the skin. They just stick in the hair. But after an injury, they will migrate up and contribute to the reforming of the epidermis or the top layer of the skin.
MATTISON: So all these cells are rushing to the scene to cover the wound and regrow or regenerate the skin.
MOLLY BLOOM: And not only are the cells migrating, they're also proliferating.
MATTISON: This is when the cells make copies of themselves.
VALERIE HORSLEY: So pretty much everything is proliferating, pretty much every cell type is doing that.
DERMIS: We need some more cells.
CELLS: Coming up.
DERMIS: Copying that, DNA?
DNA: Copying.
DERMIS: Dividing?
DNA: Dividing. Here we go. 3, 2, 1.
MOLLY BLOOM: The original cell is known as the mother cell, and the copy is known as the daughter cell.
DAUGHTER CELL: Hi, mother.
MOTHER CELL: Yes. Hello, dear. Now, run along and please get to work, kid. We have a wound to heal.
MOLLY BLOOM: Depending on the size of the wound, the process of regeneration takes about seven days.
MATTISON: Then, remodeling that repaired area can take weeks or even months.
MOLLY BLOOM: But the skin that is made after a wound is a little different than your other uninjured skin.
VALERIE HORSLEY: So the fibroblasts, they can't really make that support network exactly like they did when the skin was formed. And so, that's what scarring is that the support network is a little different. And so that's why the skin looks a little different.
The other thing is that the skin also has what we call appendages which are like hair follicles, and sweat glands, and sebaceous glands, which make the oil for the skin surface. And we don't really know how to make those during wound healing.
MOLLY BLOOM: So next time you get a cut, think about all the cells rushing in to help make sure your skin is intact so it can continue to protect your body from the outside world.
GROUP: Ba, ba, ba, ba, ba, ba, ba, ba, ba, ba, ba, Brains On.
MOLLY BLOOM: Valerie mentioned something called stem cells when she explained how skin heals, and we want to look a little closer at these amazing cells.
MATTISON: Stem cells are crucial to how our bodies heal. And to find out more about them, we talked to scientist Meri Firpo from the University of Minnesota Stem Cell Institute. I asked her, what are stem cells?
MERI FIRPO: Stem cells are very special cells, and they're very rare cells in our body. And they're sprinkled throughout our body, and they act as a reservoir of cells. And like a reservoir that holds water, these cells aren't really being used yet, but they're being saved for later times if they need to be used for replacing cells that are lost through aging, or injury, or infection.
MATTISON: Mary told us that stem cells are basically blank slates. They have the potential to become any kind of cell.
MERI FIRPO: They're relatively small. And because they don't have a real function yet, they're not red with hemoglobin, like red blood cells, and they aren't stretched out like a muscle cell because they haven't been specified on what they're going to do. They tend to be quite small and not very interesting-looking.
Any tissue that can regenerate or make more cells, there are stem cells there. And some tissues that have a lot of regeneration, for example, your skin and your hair that are constantly growing and replacing themselves, there are lots of stem cells. In other cases, for example, in your bone marrow, the stem cells are really very rare and hard to find.
MOLLY BLOOM: When a stem cell becomes a certain kind of cell that has a function in the body, this is called differentiation.
MATTISON: How are they involved in healing?
MERI FIRPO: Well, stem cells are very important for healing. And in fact, in the first stages of healing after an injury, for example, say, if you get a cut in your skin, there are cells that either clot the blood so that you don't bleed and cells that knit together and form a scab.
After that point, then the stem cells have time to go through a process we call differentiation and make mature cells that replace the cells that are lost and fix the injury. And they can do the same thing after infection or other types of cell death, like cells that have died through the aging process.
MATTISON: What does scientists use stem cells for?
MERI FIRPO: Well, we use stem cells for lots of things, and we study stem cells in the laboratory in a way that we can understand human development and human diseases, because we can take the stem cells and allow them to differentiate in the lab.
MATTISON: In her lab, Mary and her team can make stem cells out of any cells.
MOLLY BLOOM: They usually use skin cells to do so, but scientists have also used blood or even eyelashes to make stem cells.
MERI FIRPO: Well, it's a pretty exciting process, and we've only had it for less than 10 years. And the way that it works is that you take genes that are expressed in stem cells but not non-stem cells. And you put them into the skin cells that you've collected, and it turns the skin cells permanently into stem cells. And we can do this in various different ways.
But usually, we use little tiny viruses to bring those genes into the cells. And then those cells, we can grow them pretty much forever in the laboratory once they're stem cells. And we can also put them in a deep freeze to keep them for when the patient needs them.
MATTISON: Once they've made these stem cells, called pluripotent cells, they can turn them into whatever kind of cell they like.
MOLLY BLOOM: The way this is done is to feed the cells certain things and provide it with certain growth factors. So to recap, scientists take a normal cell, insert it with some stem cell genes. That cell then turns into a stem cell, then researchers work with that stem cell to change it into whatever kind of cell they want.
MATTISON: In Meri's lab, where they're trying to find treatments for diabetes, they use this process to grow insulin-producing cells. They're called beta cells.
MERI FIRPO: They go from unspecified to being specified to the internal organs, and then being more specified to the pancreas, and then to the insulin-producing cells. So it's a sequential process, and it takes a couple of weeks from the stem cell to the cells that we transplant. We're trying to reproduce in the laboratory what happens naturally when the pancreas and the insulin-producing cells in the pancreas are generated during our development.
MATTISON: There's a lot of research being done with stem cells in many different areas.
MERI FIRPO: Well, stem cell research is a relatively new area of science, and there's lots of interesting things to do and lots of exciting things that need to be done. So we need lots of new scientists to help us with new ideas and come up with new understanding of our cells, the world, and also to make new cures for diseases that don't have cures.
[MUSIC PLAYING]
MOLLY BLOOM: Hey, Matty, are you ready for a challenge?
MATTISON: Yep.
MOLLY BLOOM: OK, here comes the mystery sound.
[MUSIC PLAYING]
CHILD: (WHISPERING) Mystery sound.
MOLLY BLOOM: This sound is short, so get ready.
MATTISON: OK.
[MYSTERY SOUND]
MOLLY BLOOM: Let's hear it again.
[MYSTERY SOUND]
MOLLY BLOOM: Any guesses?
MATTISON: Sounds like the sound of one like a sword. It's like pulled out of its sheath.
MOLLY BLOOM: That is an excellent guess. I'm going to give you a hint. It's actually a sound from a character in a movie, and it has to do with healing. So let's hear it one more time.
[MYSTERY SOUND]
MOLLY BLOOM: We'll be back with the answer in just a bit.
SANDEN TOTTEN: Hey, producer Sanden Totten here.
MARC SANCHEZ: And producer Marc Sanchez.
BOB: And me, Bob.
SANDEN TOTTEN: Not now, Bob.
BOB: Oh, wait. But, but--
SANDEN TOTTEN: Just wait. Just wait, Bob. And can you hold the microphone?
BOB: Oh, like this?
MARC SANCHEZ: No, that's too far. I got to get closer to my mouth.
BOB: So, like this?
MARC SANCHEZ: Not in my mouth, Bob.
BOB: Oh, I got it. Hold on.
SANDEN TOTTEN: OK, OK, that's good. That's good. Just stay steady.
BOB: All right.
SANDEN TOTTEN: Now, where was I? Oh, yeah. Hey, you listen to Brains On so that means you have something really valuable to us.
MARC SANCHEZ: Your thoughts about the show.
SANDEN TOTTEN: We're working with the National Science Foundation to make Brains On even better. And we'd love to hear from you.
MARC SANCHEZ: How do you listen? Why do you listen? What are you taking away from the show? We want to know. You can really help us out by answering a short survey online or by signing up to be part of family interviews.
SANDEN TOTTEN: And you'll get a cool thank you surprise for helping us out. Just go to brainson.org/supoernova. That's brainson.org/super-- N-O-V-A.
MARC SANCHEZ: Thanks, and high fives for the help. OK, Bob, now you can talk.
BOB: Finally. Your questions, drawings, mystery sounds, and high fives fuel our show. We love and appreciate everything you send in.
SANDEN TOTTEN: So if you want to get in touch, email us at hellobrainson.org.
MARC SANCHEZ: That's just what Lilith did when she sent us this question.
LILY: How do frog's tongue stretch so far?
BOB: To hear the answer, stick around. You get it? Stick because the tongue is--
SANDEN TOTTEN: Yep, we got it, Bob. Thanks. That answer and the Brains Honor Roll all at the end of the show. Keep listening. Hey, good work, Bob.
BOB: Well, thanks. I think I should host. I'm pretty good.
MOLLY BLOOM: You're listening to Brains On from American Public Media.
MATTISON: I'm Mattison.
MOLLY BLOOM: And I'm Molly Bloom. OK, let's get back to the business of the mystery sound. Here it is one more time.
[MYSTERY SOUND]
Any final guesses?
MATTISON: Is it the Wolverine?
MOLLY BLOOM: From X-Men?
MATTISON: Yeah. Well, let's find out if you're right. Here with the answer is Matt Key from the Marvel Movie News podcast.
MATT KEY: That sound you just heard was Wolverine's claws popping out, and that was from the X-Men movies.
MOLLY BLOOM: So you're right. For those of you who don't know, Wolverine is a superhero from comics, cartoons, and movies, and Matt Key is going to tell us about his powers which fit with our episode today.
MATT KEY: His powers are that he has superhuman healing ability, regenerative ability, which allows him to recover very quickly from pretty much any wound. What he's more famously known for are his claws that he can pop out of his hands, and they are razor sharp. His healing powers allow him to come back from almost any injury.
Like, no matter how many times you cut at him or knock him down, he's always able to get back up and come right back. So he's this impossible force of nature. He's actually born in the middle of the 19th century, so he's very old. And his healing ability has allowed him to heal that entire time and not really age too much.
He's fought in World War I, World War II. He's fought in Vietnam. He's always been a soldier, all because of his healing abilities. He was born with a fountain of youth inside of him in some way. It's a comic book world, so we really don't get too much of an explanation of how it works. We we're just told that it does.
MOLLY BLOOM: Now, obviously, Wolverine is a fictional character in a comic book.
MATTISON: But there are some real life creatures that have the ability to regenerate body parts.
MOLLY BLOOM: Starfish or sea stars can do it.
MATTISON: So can worms, and so can the salamander.
MOLLY BLOOM: Brains On listener Alex sent us a question about a specific type of salamander called an axolotl.
ALEX: Hi. My name is Alex, and I'm 11 years old. My question is, how do axolotls grow back their limbs?
MATTISON: Producer Marc Sanchez is here with the salamander story.
MARC SANCHEZ: Thanks, Molly and Matty. And hello, salamander.
SALAMANDER: Hola, I am the salamander. Buenos dias.
MARC SANCHEZ: It's true. Our amphibian friend, the salamander, has the Wolverine-like ability to regrow his limbs. And interesting fact-- mammals, like us humans, have a lot of the same genes as salamanders. And except for the whole regeneration thing, the way salamanders heal is pretty much like us.
Let's go back now to before you were born. You were just a little blueberry-sized jumble of cells in your mother's belly, an embryo. And it's about at this stage that embryos start to develop little paddle-like knobs that will turn into limbs. We don't just start off with fully-formed arms and legs.
DAVID GARDINER: All of us develop as embryos, and our arms and legs develop through these outgrowths that we call limb buds. And they grow, and then they go through changes, shape changes, and they differentiate to make muscle and bone, and nerves. And eventually, we have arms and legs.
MARC SANCHEZ: David Gardiner is a professor of developmental and cell biology at UC Irvine. His lab studies this process. Or actually, they study the salamander.
DAVID GARDINER: So in the salamander, these very early signals recreate the equivalent of a limb bud. And then it goes through that same process that happened in the embryo, and it remakes the arm and leg or whatever part you've cut off. And that's what we call regeneration.
And of course, we don't do that. It turns out, almost all the bits and pieces can regenerate. So muscle regenerates, and blood vessels regenerate, and nerves can regenerate. But somehow or other, the complex structure fails to form. And so, we heal the wound which is really important, but it forms a scar.
MARC SANCHEZ: Let's say, our salamander friend meets up with one of his natural predators-- the skunk.
SALAMANDER: Man, you stink.
MARC SANCHEZ: But before he can run away, the skunk bites his tail.
SALAMANDER: I don't really need that thing. Think of it as a gift from me to you. Adios.
MARC SANCHEZ: The tail stays with the skunk, and our taillless salamander runs away to safety.
SALAMANDER: You win some. You lose some. Me, I can afford to lose some. Don't get me wrong, though, my backside kind of hurts.
MARC SANCHEZ: Like David was just saying, if something like this happened to us, this is the point where we would begin to seal off the wound and grow a scar. Our bodies essentially say, OK, we've been hurt at this spot. Let's close it up for good. Think of a scar as a plaque you might see at a memorial site.
SPEAKER 3: This scar represents a hard-fought battle. Many cells courageously came together, stopped the bleeding, and covered this wound. May we never forget their bravery.
MARC SANCHEZ: OK, maybe that's a little dramatic, but you get the point. Nothing comes back to the scar site. After our salamanders wound is covered, his body kicks into action. No memorial plaque. Remember those embryonic limb buds David was talking about earlier? Well, the salamander triggers something similar. It's called a blastema. A blastema is this big group of cells that form at the wound site, and these cells can basically be told to turn into anything.
BLASTEMA 1: I could be anything.
BLASTEMA 2: I could be anything.
BLASTEMA 3: I can be anything, too.
BLASTEMA 4: I can be anything.
MARC SANCHEZ: Underneath the freshly-covered wound, even the cells that have already differentiated into things like muscle or bone, those cells can de-differentiate back into a blastema.
BLASTEMAS: Anything. Anything. Anything. Anything. Anything. Anything. Anything.
MARC SANCHEZ: And after about four or five days, the cells in a blastema get their marching orders.
BLASTEMA 5: You there.
BLASTEMA 6: Sir, yes, sir.
BLASTEMA 5: You're going to be a new muscle cell.
BLASTEMA 6: Sir, yes, sir.
BLASTEMA 5: And you.
BLASTEMA 7: Sir, yes, sir.
BLASTEMA 5: We're going to need you to help grow some bones.
BLASTEMA 7: Sir, yes, sir.
BLASTEMA 5: OK, move out.
MARC SANCHEZ: Right now, scientists, like David Gardiner, have a really good grasp on the process of what's going on in the salamander, you know, how it regenerates its limb.
SALAMANDER: Pretty cool, right?
MARC SANCHEZ: The question is how to get our cells to behave like the salamanders?
DAVID GARDINER: Everything we know about blastema cells, they are the same as embryonic cells that made the limb in the first place. That's really important because what that says is, maybe we don't regenerate because we don't have the right genes, but that doesn't make sense.
Because if regeneration is a redeveloping, and you have the genes that make an arm in the first place, which we do, because we all have them, then we have the genes to remake it. It's just how do you re-access, go back and access those genes that were there, inactive in the embryo, and turn them on again and have them remake the limb in the adult.
MARC SANCHEZ: Our cells regenerate all the time. Those skin cells on the tip of your fingers are completely different from the cells that were there about a month ago. When our muscle cells become injured, same thing. They are replaced with regenerated muscle cells. But--
DAVID GARDINER: There's two parts to it. There's the bits and pieces.
MARC SANCHEZ: Muscle cells from muscle cell.
DAVID GARDINER: But you also have to have information. It's like a blueprint when you make a house. Most of the bits and pieces of our body actually regenerate really, really well. So where we probably aren't getting it is how do we control the information. And what that involves is we have to learn how to talk to cells. They clearly communicate to each other. We're trying to unlock or learn the language that the cells use.
MARC SANCHEZ: And if we know that language, then we can tell the cells what to do.
DAVID GARDINER: Rather than to make scars to make a blastema, and the blastema will go on and regenerate the missing body part. Because that's the way we think about it, right? Talk to the cells. Listen to what the cells have to say. Learn the language.
MARC SANCHEZ: OK, think about what we can do if we learn the language. Growing back limbs like the salamander or Wolverine, that's just the beginning. We can only see the scars on top of our skin, but there are scars inside our bodies, too.
Vital organs, like the liver, or heart, or the brain, they can become scarred, so much so that, sometimes, they don't function properly or just stop working altogether. That's bad. But what if, instead of forming scars, we were capable of regenerating these organs? With any luck, that's what our pal, the salamander, can teach us.
MATTISON: Thanks Mark, and thanks, salamander.
SALAMANDER: You're welcome. De nada.
MOLLY BLOOM: There's a lot of research going on about how we heal.
MATTISON: And how we can harness the power of some of our cells to cure disease.
MOLLY BLOOM: Some scientists are even trying to figure out how we can be more like salamanders.
MATTISON: And maybe regenerate our own limbs someday.
MATTISON: That's it for this episode of Brains On.
MATTISON: This episode was produced by Marc Sanchez, Sanden Totten, and Molly Bloom.
MOLLY BLOOM: Many thanks to Barb and Jackson and to our many voice actors, Larissa Anderson, Hans Buetow, John Miller, Valerie Keller, Linda Singh, Edgar Aguirre, Mike Edgerley, Vicki Crickler, Meg Martin, Michael Olson, Mike Mulcahy, Curtis Gilbert, Tracy Mumford, Julie Seiple, and Nancy Yang. Now, before we go, it's time for our moment of um..
LILY: Hi, I'm Lily from Washington State. And my question is, how do frog's tongue stretch so far?
KIISA NISHIKAWA: My name is Kiisa Nishikawa, and I'm a professor at Northern Arizona University. We did a lot of work, making, actually, high speed movies. I think we looked at, probably, over 120 different species of frogs from all over the world. So we learned a lot about how different frogs catch bugs and the different biomechanics of their mouths and tongues and how that allows them to move really, really fast to catch a bug.
The only real benefit that we could find from field studies, looking at how these frogs catch bugs with different types of tongues, was really that they could catch bugs at some distance from their mouth without having to jump with their whole bodies to catch them so that they would be less noticeable to the predators in that environment.
Frogs have pretty long tongues, much longer, for example, than our tongues. But they are, by no means, the record holders. Chameleons have the longest tongues, and their tongues can be twice the length of their bodies, which is pretty scary when you think about it.
I think the longest frog tongues are probably on the order of about a third of the body length, a third to a half of the body length. And of course, frogs, compared to salamanders and chameleons, have short little bodies, that they aren't as elongated.
MOLLY BLOOM: My tongue won't get tired as I speed through this list of names it's time for the latest group to be added to the Brains Honor Roll. These are the kids who fuel this show with their energy and ideas.
[LISTING HONOR ROLL]
Remember, if you want to be added to the Brains Honor roll, you can send your questions, drawings, and mystery sounds anytime to hello@brainson.org. We'll be back soon with more answers to your questions.
MATTISON: Thanks for listening.
SPEAKER 2: Brains On is supported, in part, by a grant from the National Science Foundation.
[MUSIC PLAYING]
MOLLY BLOOM: We all get cuts and scrapes.
MATTISON: And we all know what happens.
MOLLY BLOOM: You get a scab-- try not to pick at it-- then after a little while, the cut heals.
MATTISON: Sometimes, you're left with a cool-looking scar.
MOLLY BLOOM: But what's really going on when you heal?
MATTISON: What superpowers does your skin have?
MOLLY BLOOM: And what about other animals--
MATTISON: Like salamanders.
MOLLY BLOOM: --that can do some pretty extreme healing.
MATTISON: We're going under the skin for this one, so keep listening.
MOLLY BLOOM: You're listening to Brains On from American Public Media. I'm Molly Bloom, and here with me today is 12-year-old Mattison. From St. Paul.
MATTISON: Hi, Molly.
MOLLY BLOOM: Now, Matty, you are interested in finding out more about healing, and you even hope to help with that for a job one day. Is that right?
MATTISON: Yeah, so I want to be a surgeon.
MOLLY BLOOM: Very cool. What specific kind of surgeon?
MATTISON: Yeah, like a sports medical orthopedic surgeon.
MOLLY BLOOM: Wow. And what got you interested in that job?
MATTISON: Well, I've always been interested in medicine and medical stuff as a kid because my mom's a nurse, so she's led me into that background.
MOLLY BLOOM: Very cool. So I'm guessing you don't get grossed out very easily.
MATTISON: No.
MOLLY BLOOM: That's good.
MATTISON: Yeah.
MOLLY BLOOM: Well, today, we're going to learn about the process that your future patients and pretty much everyone else, for that matter, goes through when they heal.
MATTISON: We're starting with the question that was sent to us from Leo in Saint Paul, Minnesota.
LEO: When a person gets hurt, how does the skin grow back?
MOLLY BLOOM: We talked to Valerie Horsley to find out.
MATTISON: She's a scientist at Yale University, who studies skin development and regeneration after injury.
MOLLY BLOOM: After you get a cut, the healing process starts right away.
VALERIE HORSLEY: Really, your skin wants to make a barrier, like a Saran wrap over your body. And if there's some hole in that Saran wrap, then your body really wants to repair that hole.
MOLLY BLOOM: When you first get a cut, there are a few things that happen right away.
MATTISON: Your blood vessels constrict, helping to stop the blood flow.
MOLLY BLOOM: Then special cells in your blood, called platelets, rushed to the scene to form a clot.
PLATELET: Here we come. Don't worry, we'll stick together.
MOLLY BLOOM: These platelets start secreting proteins that send messages to different cells.
MATTISON: First, these proteins join up with fibrin.
MOLLY BLOOM: It's a thread-like protein. Imagine little strings in your blood.
FIBRIN: Have no fears, guys. Team fibrin is here. We'll help you finish this clot.
PLATELET: All right, the, gang's all here.
MATTISON: The platelets and the thread-like fibrin join together to form a mesh of material that becomes a scab.
PLATELET: You go there.
FIBRIN: And I'll go over there.
PLATELET: It looks like it's holding.
FIBRIN: Go, us.
VALERIE HORSLEY: Your skin is there to protect your body from the outside environment, keeps bacteria out, viruses out. So the scab is there to protect you from your outside environment. And it's there, really, to just seal over the area like a Band-Aid while everything else is repairing underneath it.
MOLLY BLOOM: There's a lot going on under that scab to repair your skin.
MATTISON: White blood cells come to destroy any germs that may have snuck in the open wound.
WHITE BLOOD CELLS: Bacteria, be gone.
MATTISON: Meanwhile, your platelets send out another signal.
MOLLY BLOOM: This one goes to cells in the skin, called keratinocytes.
FIBRIN: Hey, keratinocytes, we need you over here.
MOLLY BLOOM: Those cells, which make up the top layer of your skin--
MATTISON: Called epidermis.
MOLLY BLOOM: --start migrating to the wound.
KERATINOCYTES: We're coming. Just a sec.
MATTISON: Another signal tell cells in the bottom layer of skin--
MOLLY BLOOM: Called the dermis.
MATTISON: --to migrate over as well.
DERMIS: Fibroblasts, do your thing. We need you over here.
FRIBROBLAST: We hear you. On our way.
MATTISON: These fibroblasts make up the support network under the top layer of skin.
MOLLY BLOOM: It's really an all hands on deck situation. All the cells nearby that can help are called into service.
VALERIE HORSLEY: So we know that there are stem cells in the hair follicles. And normally, they don't go up into the top layer of the skin. They just stick in the hair. But after an injury, they will migrate up and contribute to the reforming of the epidermis or the top layer of the skin.
MATTISON: So all these cells are rushing to the scene to cover the wound and regrow or regenerate the skin.
MOLLY BLOOM: And not only are the cells migrating, they're also proliferating.
MATTISON: This is when the cells make copies of themselves.
VALERIE HORSLEY: So pretty much everything is proliferating, pretty much every cell type is doing that.
DERMIS: We need some more cells.
CELLS: Coming up.
DERMIS: Copying that, DNA?
DNA: Copying.
DERMIS: Dividing?
DNA: Dividing. Here we go. 3, 2, 1.
MOLLY BLOOM: The original cell is known as the mother cell, and the copy is known as the daughter cell.
DAUGHTER CELL: Hi, mother.
MOTHER CELL: Yes. Hello, dear. Now, run along and please get to work, kid. We have a wound to heal.
MOLLY BLOOM: Depending on the size of the wound, the process of regeneration takes about seven days.
MATTISON: Then, remodeling that repaired area can take weeks or even months.
MOLLY BLOOM: But the skin that is made after a wound is a little different than your other uninjured skin.
VALERIE HORSLEY: So the fibroblasts, they can't really make that support network exactly like they did when the skin was formed. And so, that's what scarring is that the support network is a little different. And so that's why the skin looks a little different.
The other thing is that the skin also has what we call appendages which are like hair follicles, and sweat glands, and sebaceous glands, which make the oil for the skin surface. And we don't really know how to make those during wound healing.
MOLLY BLOOM: So next time you get a cut, think about all the cells rushing in to help make sure your skin is intact so it can continue to protect your body from the outside world.
GROUP: Ba, ba, ba, ba, ba, ba, ba, ba, ba, ba, ba, Brains On.
MOLLY BLOOM: Valerie mentioned something called stem cells when she explained how skin heals, and we want to look a little closer at these amazing cells.
MATTISON: Stem cells are crucial to how our bodies heal. And to find out more about them, we talked to scientist Meri Firpo from the University of Minnesota Stem Cell Institute. I asked her, what are stem cells?
MERI FIRPO: Stem cells are very special cells, and they're very rare cells in our body. And they're sprinkled throughout our body, and they act as a reservoir of cells. And like a reservoir that holds water, these cells aren't really being used yet, but they're being saved for later times if they need to be used for replacing cells that are lost through aging, or injury, or infection.
MATTISON: Mary told us that stem cells are basically blank slates. They have the potential to become any kind of cell.
MERI FIRPO: They're relatively small. And because they don't have a real function yet, they're not red with hemoglobin, like red blood cells, and they aren't stretched out like a muscle cell because they haven't been specified on what they're going to do. They tend to be quite small and not very interesting-looking.
Any tissue that can regenerate or make more cells, there are stem cells there. And some tissues that have a lot of regeneration, for example, your skin and your hair that are constantly growing and replacing themselves, there are lots of stem cells. In other cases, for example, in your bone marrow, the stem cells are really very rare and hard to find.
MOLLY BLOOM: When a stem cell becomes a certain kind of cell that has a function in the body, this is called differentiation.
MATTISON: How are they involved in healing?
MERI FIRPO: Well, stem cells are very important for healing. And in fact, in the first stages of healing after an injury, for example, say, if you get a cut in your skin, there are cells that either clot the blood so that you don't bleed and cells that knit together and form a scab.
After that point, then the stem cells have time to go through a process we call differentiation and make mature cells that replace the cells that are lost and fix the injury. And they can do the same thing after infection or other types of cell death, like cells that have died through the aging process.
MATTISON: What does scientists use stem cells for?
MERI FIRPO: Well, we use stem cells for lots of things, and we study stem cells in the laboratory in a way that we can understand human development and human diseases, because we can take the stem cells and allow them to differentiate in the lab.
MATTISON: In her lab, Mary and her team can make stem cells out of any cells.
MOLLY BLOOM: They usually use skin cells to do so, but scientists have also used blood or even eyelashes to make stem cells.
MERI FIRPO: Well, it's a pretty exciting process, and we've only had it for less than 10 years. And the way that it works is that you take genes that are expressed in stem cells but not non-stem cells. And you put them into the skin cells that you've collected, and it turns the skin cells permanently into stem cells. And we can do this in various different ways.
But usually, we use little tiny viruses to bring those genes into the cells. And then those cells, we can grow them pretty much forever in the laboratory once they're stem cells. And we can also put them in a deep freeze to keep them for when the patient needs them.
MATTISON: Once they've made these stem cells, called pluripotent cells, they can turn them into whatever kind of cell they like.
MOLLY BLOOM: The way this is done is to feed the cells certain things and provide it with certain growth factors. So to recap, scientists take a normal cell, insert it with some stem cell genes. That cell then turns into a stem cell, then researchers work with that stem cell to change it into whatever kind of cell they want.
MATTISON: In Meri's lab, where they're trying to find treatments for diabetes, they use this process to grow insulin-producing cells. They're called beta cells.
MERI FIRPO: They go from unspecified to being specified to the internal organs, and then being more specified to the pancreas, and then to the insulin-producing cells. So it's a sequential process, and it takes a couple of weeks from the stem cell to the cells that we transplant. We're trying to reproduce in the laboratory what happens naturally when the pancreas and the insulin-producing cells in the pancreas are generated during our development.
MATTISON: There's a lot of research being done with stem cells in many different areas.
MERI FIRPO: Well, stem cell research is a relatively new area of science, and there's lots of interesting things to do and lots of exciting things that need to be done. So we need lots of new scientists to help us with new ideas and come up with new understanding of our cells, the world, and also to make new cures for diseases that don't have cures.
[MUSIC PLAYING]
MOLLY BLOOM: Hey, Matty, are you ready for a challenge?
MATTISON: Yep.
MOLLY BLOOM: OK, here comes the mystery sound.
[MUSIC PLAYING]
CHILD: (WHISPERING) Mystery sound.
MOLLY BLOOM: This sound is short, so get ready.
MATTISON: OK.
[MYSTERY SOUND]
MOLLY BLOOM: Let's hear it again.
[MYSTERY SOUND]
MOLLY BLOOM: Any guesses?
MATTISON: Sounds like the sound of one like a sword. It's like pulled out of its sheath.
MOLLY BLOOM: That is an excellent guess. I'm going to give you a hint. It's actually a sound from a character in a movie, and it has to do with healing. So let's hear it one more time.
[MYSTERY SOUND]
MOLLY BLOOM: We'll be back with the answer in just a bit.
SANDEN TOTTEN: Hey, producer Sanden Totten here.
MARC SANCHEZ: And producer Marc Sanchez.
BOB: And me, Bob.
SANDEN TOTTEN: Not now, Bob.
BOB: Oh, wait. But, but--
SANDEN TOTTEN: Just wait. Just wait, Bob. And can you hold the microphone?
BOB: Oh, like this?
MARC SANCHEZ: No, that's too far. I got to get closer to my mouth.
BOB: So, like this?
MARC SANCHEZ: Not in my mouth, Bob.
BOB: Oh, I got it. Hold on.
SANDEN TOTTEN: OK, OK, that's good. That's good. Just stay steady.
BOB: All right.
SANDEN TOTTEN: Now, where was I? Oh, yeah. Hey, you listen to Brains On so that means you have something really valuable to us.
MARC SANCHEZ: Your thoughts about the show.
SANDEN TOTTEN: We're working with the National Science Foundation to make Brains On even better. And we'd love to hear from you.
MARC SANCHEZ: How do you listen? Why do you listen? What are you taking away from the show? We want to know. You can really help us out by answering a short survey online or by signing up to be part of family interviews.
SANDEN TOTTEN: And you'll get a cool thank you surprise for helping us out. Just go to brainson.org/supoernova. That's brainson.org/super-- N-O-V-A.
MARC SANCHEZ: Thanks, and high fives for the help. OK, Bob, now you can talk.
BOB: Finally. Your questions, drawings, mystery sounds, and high fives fuel our show. We love and appreciate everything you send in.
SANDEN TOTTEN: So if you want to get in touch, email us at hellobrainson.org.
MARC SANCHEZ: That's just what Lilith did when she sent us this question.
LILY: How do frog's tongue stretch so far?
BOB: To hear the answer, stick around. You get it? Stick because the tongue is--
SANDEN TOTTEN: Yep, we got it, Bob. Thanks. That answer and the Brains Honor Roll all at the end of the show. Keep listening. Hey, good work, Bob.
BOB: Well, thanks. I think I should host. I'm pretty good.
MOLLY BLOOM: You're listening to Brains On from American Public Media.
MATTISON: I'm Mattison.
MOLLY BLOOM: And I'm Molly Bloom. OK, let's get back to the business of the mystery sound. Here it is one more time.
[MYSTERY SOUND]
Any final guesses?
MATTISON: Is it the Wolverine?
MOLLY BLOOM: From X-Men?
MATTISON: Yeah. Well, let's find out if you're right. Here with the answer is Matt Key from the Marvel Movie News podcast.
MATT KEY: That sound you just heard was Wolverine's claws popping out, and that was from the X-Men movies.
MOLLY BLOOM: So you're right. For those of you who don't know, Wolverine is a superhero from comics, cartoons, and movies, and Matt Key is going to tell us about his powers which fit with our episode today.
MATT KEY: His powers are that he has superhuman healing ability, regenerative ability, which allows him to recover very quickly from pretty much any wound. What he's more famously known for are his claws that he can pop out of his hands, and they are razor sharp. His healing powers allow him to come back from almost any injury.
Like, no matter how many times you cut at him or knock him down, he's always able to get back up and come right back. So he's this impossible force of nature. He's actually born in the middle of the 19th century, so he's very old. And his healing ability has allowed him to heal that entire time and not really age too much.
He's fought in World War I, World War II. He's fought in Vietnam. He's always been a soldier, all because of his healing abilities. He was born with a fountain of youth inside of him in some way. It's a comic book world, so we really don't get too much of an explanation of how it works. We we're just told that it does.
MOLLY BLOOM: Now, obviously, Wolverine is a fictional character in a comic book.
MATTISON: But there are some real life creatures that have the ability to regenerate body parts.
MOLLY BLOOM: Starfish or sea stars can do it.
MATTISON: So can worms, and so can the salamander.
MOLLY BLOOM: Brains On listener Alex sent us a question about a specific type of salamander called an axolotl.
ALEX: Hi. My name is Alex, and I'm 11 years old. My question is, how do axolotls grow back their limbs?
MATTISON: Producer Marc Sanchez is here with the salamander story.
MARC SANCHEZ: Thanks, Molly and Matty. And hello, salamander.
SALAMANDER: Hola, I am the salamander. Buenos dias.
MARC SANCHEZ: It's true. Our amphibian friend, the salamander, has the Wolverine-like ability to regrow his limbs. And interesting fact-- mammals, like us humans, have a lot of the same genes as salamanders. And except for the whole regeneration thing, the way salamanders heal is pretty much like us.
Let's go back now to before you were born. You were just a little blueberry-sized jumble of cells in your mother's belly, an embryo. And it's about at this stage that embryos start to develop little paddle-like knobs that will turn into limbs. We don't just start off with fully-formed arms and legs.
DAVID GARDINER: All of us develop as embryos, and our arms and legs develop through these outgrowths that we call limb buds. And they grow, and then they go through changes, shape changes, and they differentiate to make muscle and bone, and nerves. And eventually, we have arms and legs.
MARC SANCHEZ: David Gardiner is a professor of developmental and cell biology at UC Irvine. His lab studies this process. Or actually, they study the salamander.
DAVID GARDINER: So in the salamander, these very early signals recreate the equivalent of a limb bud. And then it goes through that same process that happened in the embryo, and it remakes the arm and leg or whatever part you've cut off. And that's what we call regeneration.
And of course, we don't do that. It turns out, almost all the bits and pieces can regenerate. So muscle regenerates, and blood vessels regenerate, and nerves can regenerate. But somehow or other, the complex structure fails to form. And so, we heal the wound which is really important, but it forms a scar.
MARC SANCHEZ: Let's say, our salamander friend meets up with one of his natural predators-- the skunk.
SALAMANDER: Man, you stink.
MARC SANCHEZ: But before he can run away, the skunk bites his tail.
SALAMANDER: I don't really need that thing. Think of it as a gift from me to you. Adios.
MARC SANCHEZ: The tail stays with the skunk, and our taillless salamander runs away to safety.
SALAMANDER: You win some. You lose some. Me, I can afford to lose some. Don't get me wrong, though, my backside kind of hurts.
MARC SANCHEZ: Like David was just saying, if something like this happened to us, this is the point where we would begin to seal off the wound and grow a scar. Our bodies essentially say, OK, we've been hurt at this spot. Let's close it up for good. Think of a scar as a plaque you might see at a memorial site.
SPEAKER 3: This scar represents a hard-fought battle. Many cells courageously came together, stopped the bleeding, and covered this wound. May we never forget their bravery.
MARC SANCHEZ: OK, maybe that's a little dramatic, but you get the point. Nothing comes back to the scar site. After our salamanders wound is covered, his body kicks into action. No memorial plaque. Remember those embryonic limb buds David was talking about earlier? Well, the salamander triggers something similar. It's called a blastema. A blastema is this big group of cells that form at the wound site, and these cells can basically be told to turn into anything.
BLASTEMA 1: I could be anything.
BLASTEMA 2: I could be anything.
BLASTEMA 3: I can be anything, too.
BLASTEMA 4: I can be anything.
MARC SANCHEZ: Underneath the freshly-covered wound, even the cells that have already differentiated into things like muscle or bone, those cells can de-differentiate back into a blastema.
BLASTEMAS: Anything. Anything. Anything. Anything. Anything. Anything. Anything.
MARC SANCHEZ: And after about four or five days, the cells in a blastema get their marching orders.
BLASTEMA 5: You there.
BLASTEMA 6: Sir, yes, sir.
BLASTEMA 5: You're going to be a new muscle cell.
BLASTEMA 6: Sir, yes, sir.
BLASTEMA 5: And you.
BLASTEMA 7: Sir, yes, sir.
BLASTEMA 5: We're going to need you to help grow some bones.
BLASTEMA 7: Sir, yes, sir.
BLASTEMA 5: OK, move out.
MARC SANCHEZ: Right now, scientists, like David Gardiner, have a really good grasp on the process of what's going on in the salamander, you know, how it regenerates its limb.
SALAMANDER: Pretty cool, right?
MARC SANCHEZ: The question is how to get our cells to behave like the salamanders?
DAVID GARDINER: Everything we know about blastema cells, they are the same as embryonic cells that made the limb in the first place. That's really important because what that says is, maybe we don't regenerate because we don't have the right genes, but that doesn't make sense.
Because if regeneration is a redeveloping, and you have the genes that make an arm in the first place, which we do, because we all have them, then we have the genes to remake it. It's just how do you re-access, go back and access those genes that were there, inactive in the embryo, and turn them on again and have them remake the limb in the adult.
MARC SANCHEZ: Our cells regenerate all the time. Those skin cells on the tip of your fingers are completely different from the cells that were there about a month ago. When our muscle cells become injured, same thing. They are replaced with regenerated muscle cells. But--
DAVID GARDINER: There's two parts to it. There's the bits and pieces.
MARC SANCHEZ: Muscle cells from muscle cell.
DAVID GARDINER: But you also have to have information. It's like a blueprint when you make a house. Most of the bits and pieces of our body actually regenerate really, really well. So where we probably aren't getting it is how do we control the information. And what that involves is we have to learn how to talk to cells. They clearly communicate to each other. We're trying to unlock or learn the language that the cells use.
MARC SANCHEZ: And if we know that language, then we can tell the cells what to do.
DAVID GARDINER: Rather than to make scars to make a blastema, and the blastema will go on and regenerate the missing body part. Because that's the way we think about it, right? Talk to the cells. Listen to what the cells have to say. Learn the language.
MARC SANCHEZ: OK, think about what we can do if we learn the language. Growing back limbs like the salamander or Wolverine, that's just the beginning. We can only see the scars on top of our skin, but there are scars inside our bodies, too.
Vital organs, like the liver, or heart, or the brain, they can become scarred, so much so that, sometimes, they don't function properly or just stop working altogether. That's bad. But what if, instead of forming scars, we were capable of regenerating these organs? With any luck, that's what our pal, the salamander, can teach us.
MATTISON: Thanks Mark, and thanks, salamander.
SALAMANDER: You're welcome. De nada.
MOLLY BLOOM: There's a lot of research going on about how we heal.
MATTISON: And how we can harness the power of some of our cells to cure disease.
MOLLY BLOOM: Some scientists are even trying to figure out how we can be more like salamanders.
MATTISON: And maybe regenerate our own limbs someday.
MATTISON: That's it for this episode of Brains On.
MATTISON: This episode was produced by Marc Sanchez, Sanden Totten, and Molly Bloom.
MOLLY BLOOM: Many thanks to Barb and Jackson and to our many voice actors, Larissa Anderson, Hans Buetow, John Miller, Valerie Keller, Linda Singh, Edgar Aguirre, Mike Edgerley, Vicki Crickler, Meg Martin, Michael Olson, Mike Mulcahy, Curtis Gilbert, Tracy Mumford, Julie Seiple, and Nancy Yang. Now, before we go, it's time for our moment of um..
LILY: Hi, I'm Lily from Washington State. And my question is, how do frog's tongue stretch so far?
KIISA NISHIKAWA: My name is Kiisa Nishikawa, and I'm a professor at Northern Arizona University. We did a lot of work, making, actually, high speed movies. I think we looked at, probably, over 120 different species of frogs from all over the world. So we learned a lot about how different frogs catch bugs and the different biomechanics of their mouths and tongues and how that allows them to move really, really fast to catch a bug.
The only real benefit that we could find from field studies, looking at how these frogs catch bugs with different types of tongues, was really that they could catch bugs at some distance from their mouth without having to jump with their whole bodies to catch them so that they would be less noticeable to the predators in that environment.
Frogs have pretty long tongues, much longer, for example, than our tongues. But they are, by no means, the record holders. Chameleons have the longest tongues, and their tongues can be twice the length of their bodies, which is pretty scary when you think about it.
I think the longest frog tongues are probably on the order of about a third of the body length, a third to a half of the body length. And of course, frogs, compared to salamanders and chameleons, have short little bodies, that they aren't as elongated.
MOLLY BLOOM: My tongue won't get tired as I speed through this list of names it's time for the latest group to be added to the Brains Honor Roll. These are the kids who fuel this show with their energy and ideas.
[LISTING HONOR ROLL]
Remember, if you want to be added to the Brains Honor roll, you can send your questions, drawings, and mystery sounds anytime to hello@brainson.org. We'll be back soon with more answers to your questions.
MATTISON: Thanks for listening.
Transcription services provided by 3Play Media.
