Tooth enamel is the strongest substance produced by the human body, protecting the sensitive lower layers of the teeth. But once it wears away, we can’t regrow it. The cells that create enamel, called ameloblasts, die shortly after the teeth are formed. New research from the University of Washington could eventually change that, however. Researchers have succeeded in transforming stem cells into ameloblasts, which can produce a rudimentary enamel under the right conditions.
Hannele Ruohola-Baker is a professor of biochemistry and associate director of the Institute for Stem Cell & Regenerative Medicine at the University of Washington. She joins us with more details on what the ability to regrow enamel could mean for dental patients.
This transcript was created by a computer and edited by a volunteer.
Dave Miller: This is Think Out Loud on OPB. I’m Dave Miller. Tooth enamel is the strongest substance produced by the human body, protecting the sensitive inner parts of our teeth. But once it’s gone, it’s gone. We only get one layer of enamel. New research from the University of Washington could eventually change that. Scientists were able to turn stem cells into specialized cells that produced a rudimentary enamel. Hannele Ruohola-Baker is a professor of biochemistry and the associate director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington. She joins us now. Welcome to Think Out Loud.
Hannele Ruohola-Baker: Thank you.
Miller: What makes tooth enamel unique among substances in the human body?
Ruohola-Baker: Well, like you said, it is the strongest material we have in our body, but enamel has its trouble. The trouble with enamel is that even though it’s so useful for us, it actually wears off. Other animals like sharks have taken care of this by producing new teeth all the time while we get our permanent teeth and then we keep the same teeth and same enamel 70 years or so in our lifetime.
Miller: Do you know why that is? Is it just that we’re living longer than our teeth were evolved to help us chew for?
Ruohola-Baker: I think you are right. We are living much longer than we used to and we perhaps ought to. But, on the other hand, we live a pretty healthy life still, into our nineties. And so it’s exciting that modern life keeps us healthy for longer. Only thing is that our teeth don’t seem to be regenerating. Our teeth are actually getting maybe more misuse than they used to. And those would be because of our food. We perhaps eat much more sugar than we ought to or we used to.
Miller: Can you describe the way tooth enamel is created normally, before you and your team started messing around in fascinating and complicated ways with stem cells? What happens normally?
Ruohola-Baker: So what happens is that actually this happens very early in you or in me or in our children – they create the teeth and particularly the dentin and enamel during the fetal development. And it basically happens in the mother’s womb. And unfortunately, some genetic diseases show up – something called amelogenesis imperfecta – mutations that can cause problems in this process in the mother’s womb, in the baby that is developing.
Miller: And am I right that by the time teeth come out of the gums, erupted, I guess is the technical word, the enamel formulation is well done by that point?
Ruohola-Baker: That’s right. So enamel is made by special cells and this cell is called ameloblast. And this ameloblast is only in our body when we are developing those teeth during the fetal development, before our permanent teeth are erupted. After that, those kinds of cells are gone. And they are needed to make enamel. So we clearly don’t have anything in our body that could make more enamel. That enamel that is produced by ameloblast in our permanent teeth got produced very early in our development. And once you have the permanent tooth erupting, like you said, there’s no more making enamel in our body.
Miller: When you first started looking into these cells, I understand that some of the first teeth you studied were actually your sons. How did that come to be?
Ruohola-Baker: That’s a good point, that I have a very personal connection to this. I work as an associate director in a stem cell institute, and I’m really interested in regeneration and stem cell-based production of different cell types. And one of these cell types, the organ that is made is our tooth. And there wasn’t really a way of analyzing, of understanding how we need to guide the stem cells to make any cell in tooth. But then it became clear that our children, both my children actually – first my daughter – entered the right of passage stage where her wisdom teeth were pulled out. And it’s a quite gruesome process actually. And then when it was my son’s turn a sort of a light bulb went on and we thought maybe we can take advantage, maybe we can turn something that isn’t so pleasant to be more pleasant.
It is true, if it’s time to get wisdom teeth pulled, you could protect cell types in there, something called dental pap stem cells. And those are stem cells that can produce part of your teeth and they can be very useful, and that was all very exciting. And, those cells, dental pap stem cells, actually can make the other interesting cell type, which is odontoblasts. And that makes the other protective layer, dentin. But unfortunately, in those teeth, you can’t find ameloblast anymore. So you really need both odontoblast and ameloblast to make the perfect tooth. You need those tools. So that’s where we went forward and realized that even though it’s very exciting to be able to analyze and understand the stem cells that exist in your wisdom teeth, it still isn’t quite enough to regenerate the tooth.
Miller: Meaning you needed embryonic stem cells to get the cells that would create enamel?
Ruohola-Baker: Right. So actually, two things there. First, we needed to understand. Like you said, my lab and the stem cell institute here in Seattle at the University of Washington is really specialized in regenerating cells from pluripotent stem cells. And today, we mainly use something called induced pluripotent stem cells. So that’s very nice. They are made by reprogramming from blood cells and they are pluripotent and you can make them from any individual who needs regeneration. So you can make these pluripotent stem cells. But now the question then was, how do we guide these pluripotent stem cells to become ameloblast?
Miller: Let me make sure that I understand and that our audience understands. So these pluripotent stem cells, these are stem cells that could turn into all kinds of cells, could turn into all kinds of organs [like] liver or brain or skin or an eyeball. And the question is how do you get them to turn into teeth? And the question for me is, can you explain how you do that in a way that we might understand?
Ruohola-Baker: Yes, actually, so we did not have the guidelines, the blueprint. We did not know what we should add to the media so that these cells would become the right kind of cell. But then we did get help from the technical development that has taken place here in Seattle, in Pacific Northwest, where people like to collaborate. There are multiple institutes. There’s the stem cell institute, there is the Institute of Protein Design and then there’s the institute for really high technology sequencing. And so we were able to analyze early human developing fetus, their RNA, the genes that are expressed in these particular cells in early stages. And now we can take our pluripotent stem cells, iPSCs, and give them either some naturally existing lichen or then use the Institute for Protein Design and use artificial intelligence to make totally new, even better molecules that make these cells take the right path.
Miller: What did you end up with? I mean, can you describe these ameloblasts – these are the cells in developing fetuses that create enamel – what did you eventually get them to create?
Ruohola-Baker: That’s a good question. So they themselves, if you let them be in a three dimensional space, they make something called organoids – they produce ameloblast that have polarity. In theory they can secrete the enamel out from one end, but they didn’t do it. So we made this great ball, organoids of the ameloblast, and we saw that the enamel proteins were made in the cells, but they didn’t come out. And that’s when we realized that’s not what happens in nature. What happens in nature is that these ameloblasts are in close contact with the other cell type, remember odontoblast. So we had to actually introduce this friend, the odontoblast, to the ameloblast organoid. And these two cells made the organoid that now began to secrete proteins that are making your enamel, the outermost material in your teeth.
Miller: So you were able to make it so that at first they made the enamel, but it wasn’t next to a necessary other cell that made something that normally would put the enamel onto. You had to actually put those together. When you say secrete, are these just sort of extruding a mess of enamel or is it making enamel, say in the shape of a tooth? Is this material you could use or is it just a finished product that is what it is?
Ruohola-Baker: Really good question and that’s exactly where we are now. So there were all these steps and hurdles, but now we are at a stage where these cells actually do what they’re supposed to be doing, secreting this protein. But now then we have to really make a tooth. And that’s where we are right now. Now we want to recruit more young scientists to join this research and sort of really become a 21st century researching dentistry lab here in University of Washington because now we see where this is leading. We actually feel like this is reality, but we are not quite there yet.
Miller: Well, what is the dream?
Ruohola-Baker: The dream is that you can use these organoids in three ways. The first dream that can come true hopefully, relatively soon, is that we have this little factory of organoids that make enamel and then we just take the enamel and paint the teeth that have little cracks with this nature-made enamel material. That would be number one. Number two is that we take the organoids and in unfortunate injuries that we get, maybe we could insert these organoids into the cavities and make them produce the right kind of material at the right place.
Miller: So there would be a filling that creates new enamel. I think I’ve seen you describe it as a living filling.
Ruohola-Baker: That’s right. I like that. Yes. I think living filling is a very refreshing way of thinking of dentistry, right?
Miller: What have you heard from dentists about this?
Ruohola-Baker: There are sort of two groups. There are lots of dentists who [see this as] very exciting. There have been two dentists who were part of this project and this paper we just published. Both of them say that they know once they see a patient with a cavity and they begin to drill the first time, they know that that’s the beginning of the tooth cycle of death. It never gets better. Things get worse and worse and as we know, we get the filling and it lasts for 10 years and then you have to do the next step and so on. So these kind of dentists are very excited about the idea that perhaps, finally, we can do something else than just fill the hole with material. But then of course, there are also the naysayers, the ones who say that this is a dream. I agree it’s a dream, but I’m a dreamer and I want to make this dream reality.
Miller: Hannele Ruohola-Baker, thanks very much for joining us.
Ruohola-Baker: Thank you. Bye.
Miller: Hannele Ruohola-Baker is a professor of biochemistry and the associate director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington.
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