Generating New Hair

How stem cells can help hair re-grow after wounding

by Amy Radermacher, Stanford University

Look at one of your scars. You'll notice some differences between a scar and the skin around it. For one, the scar isn't as stretchy as the skin. And it doesn't have any hair.

Wouldn't it be great if scientists knew how to make scars less scar-like? Well, they have taken the first step in mice.

What scientists have done is to begin to figure out how to grow hair where a scar forms. And when head scars leave bald spots being able to re-grow hair becomes pretty important. Just ask my sister.

On one of my family vacations as a kid, my sister and I were playing around on a teeter-totter. She fell off and hit her head. There was a pretty nasty gash.

So I carried her as fast as I could back to my mom and dad. They rushed her to the hospital. Luckily she didn't need any stitches.

Looking at her today, you wouldn't even know that she hit her head. Everything looks completely normal at first glance. Unless you know where to look.

As you can imagine, she has a good sized scar on the back of her head. But what you might not imagine is that she doesn't have any hair where the scar is.

The scar didn't re-grow any hair. So she has a small bald spot. She's lucky the cut wasn't any bigger. Girls don't generally look very good with large bald spots.

Hair doesn't grow no matter where a scar forms. Take a look at a couple of the scars on your body. I bet they don't have any hair.

When we get cut, scars replace normal skin so we don't have open wounds on our body. But it would be even better if we could re-grow skin like new.

The new finding helps shed light on how we might be able to re-grow hair in a scar after wounding. This will take us closer to completely healing after an accident.

How to re-grow hair

Recently, scientists stumbled onto the finding that, at least in mice, hair will sometimes re-grow after wounding. They were studying how wounds heal in mice and noticed that sometimes hair grew back. And sometimes not.

This was surprising. Why? Because scientists thought that losing hair because of scarring was permanent.

Hair follicles are like
mini-organs.

Hair grows out of hair follicles. Since hair follicles are like "mini organs," scientists thought they only formed when a fetus grows in the womb. Like how your liver or your lungs only form as a fetus.

So hair re-growing in the wounds was completely unexpected. To figure out what was going on, the scientists wounded adult mice by cutting away some of the back skin.

The wounds needed to be at least half the size of the mouse's back to form new hairs. Any smaller and hair follicles didn't form.

They weren't sure why the wound had to be that big. But they wanted to learn more about how the hair grew back in. And if the process was similar to what happens when we're in the womb.

How could the scientists answer these questions? First off, they needed to understand how hair forms in an embryo.

Turns out, we already know a lot of what is going on there. We know some of the key genes and proteins that cause hair growth.

So they looked to see if one of the key players in hair development, KRT17, was involved in growing hair after wounding. And it was.

KRT17 showed up in the new hair follicles at about the same time it would be expressed in embryonic hair follicles. So these hair follicles developed similar to embryonic hair follicles.

But the scientists knew the growth wasn't exactly the same. Why? Because the hairs always came in white. They had no pigment.

So not everything in the hair follicle grew back. The cells that have pigment, the melanocytes, didn't grow along with the rest of the hair follicle. (Like when you age and your hair turns white or gray, it's because all your melanocytes are gone.)

Alright, so can we now grow my sister's hair back after her teeter-totter accident (even if it'll be white)? Not quite. First, we need to know where the hair is coming from. And what helps it grow.

More Information

Where the hair came from

New hair comes
from stem cells.

So now we can see that the hair grows pretty similarly to what happens in the embryo. But do the hairs come from the same tissue as an embryo? In other words, do they come from hair follicle stem cells?

As adults, we have many different kinds of stem cells. Nerve stem cells. Liver, hair, blood, bone, and immune stem cells.

Each type of adult stem cell makes a specific set of cells. That means hair follicle stem cells can become any cell in a hair follicle. And form a hair follicle from scratch.

The scientists used special mice to look at the hair follicle stem cells. Treated with a chemical, the hair follicle stem cells in these mice turn blue. All the cells that come from these stem cells are also blue.

So, if the mice grow blue hair after wounding, then the hair came from hair follicle stem cells. If not, then it came from somewhere else.

The scientists treated the mice with the chemical before wounding. Just as we'd expect, all the hair follicle stem cells turned blue.

After wounding, they looked at the new hair in the wounded area. None of them were blue. So none of the hair follicles came from hair follicle stem cells.

This was unexpected. If the hair follicles weren't coming from stem cells, where were they coming from?

The scientists used another set of special mice to answer this question. In these mice, the outermost layer of skin cells (the epidermis) turns blue after treatment with the chemical.

If the new hair came from this layer of skin, then the mice would be blue-haired. If the hairs came from somewhere else, then they'd still be white.

After wounding, about half of the hairs were blue. So epidermal not hair follicle stem cells probably formed the new hairs in the wounded area.

This was a big surprise. Why? Because most adult stem cells stick to producing a small group of cells.

Take hair follicle stem cells. They produce all the parts of the hair follicle. But not the epidermis.

So epidermal stem cells should only produce parts of the epidermis. Instead, these epidermal stem cells formed all the different parts of the hair follicle.

Neat, but how does this help my sister's head scar? How can she get her hair to grow back?

One day maybe we can
regrow hair like this mouse.

Ideally, we'd like to be able to help hairs to form in scar tissue. So the scientists looked at what helps or hurts hair follicle forming in the wounded mice.

If they can figure out what is turning on the process in big wounds in mice, they may be able to mimic it in people. With smaller wounds.

They started by looking at Wnt proteins because Wnt proteins help normal hair follicles develop. They looked to see what happens in mice where they could shut off Wnt. And what happens in mice with extra Wnt protein.

If Wnt is important, we'd expect the mice without it to have hairless wounds. And maybe for the mice that make extra Wnt to have even hairier wounds. That's just what the scientists found.

After wounding, mice without Wnt didn't form hair follicles. But mice with the extra Wnt made even more hair follicles. So Wnt was very important.

We might be able to help hair follicles form in wounded regions by treating the wound with Wnt proteins before the scar forms. But we have to be careful because too much Wnt protein can sometimes lead to cancer.

Now if only we could prevent scars from forming altogether. Scientists are working on that too.

Amy Radermacher

More Information

Different types of stem cells

Content provided by the Department of Genetics, Stanford University.