Rhonda: Dr. Rhonda Patrick here. In this week's podcast, I chat with Dr. Frans Kuypers whose lab made a huge breakthrough in 2009 because they found the human placenta is a rich source of pluripotent stem cells. They also developed a technique that allowed them to retrieve between five and seven times more hematopoietic stem cells from the placenta than from cord blood, which is currently a standard technique that's used to get hematopoietic stem cells used for bone marrow transplants.

Meanwhile, the placenta is discarded and thrown away after delivery about 3.9 million times a year in the U.S. alone. The ability to retrieve between five and seven times more hematopoietic stem cells from the placenta than from cord blood is a pretty big deal in the case for bone marrow transplants, which are typically used to treat a variety of different blood cancers like leukemias and lymphomas, and also genetic blood disorders like sickle cell anemia.

In the case for blood cancers, oftentimes, chemotherapeutic treatment like radiation and other chemo drugs can wipe out the immune cells and red blood cells in the body. Hematopoietic stem cells which are multipotent, meaning they have the capacity to form different cell types in the body although they're very limited to the types of cell they can form, can repopulate the immune cells and red blood cells. So, they can form B and T lymphocytes, red blood cells, as well as other monocytes.

In addition to these hematopoietic stem cells, the placenta also has the capacity to form pluripotent stem cells, which means, these stem cells can form any type of cell in the body including blood cells, immune cells, muscle cells, lung cells, liver cells, kidney cells, brain cells. You get the point.

Before we get started, the technique that Frans and his lab developed is not consumer-available yet. Now, there are a couple of companies that do offer to freeze down and bank placenta, but they use their own methods, and we're not discussing those. So, without further ado, I hope you enjoy listening to this podcast as much as I enjoyed recording it.

Hi, guys. Thanks for joining me today. I'm pretty excited to have the opportunity to chat with Dr. Frans Kuypers who is a senior scientist at Children's Hospital Oakland Research Institute, and happens to be one of my colleagues. His current research focuses a lot on understanding the underlying mechanisms of thalassemia as well as sickle cell disease. But that's not actually why I asked him to have a chat with us today. I actually am interested in some of this previous research that has to do with the identification of a very rich source of stem cells from something that is discarded almost every day. And that source happens to be the placenta.

So, thank you for joining us, Frans. Back in 2009, your lab made a huge breakthrough, and that is that you found that the placenta is a rich source of what's called pluripotent stem cells. And for those of you that don't know what pluripotent stem cells are, what that means is that pluripotent stem cells have the capacity to form almost every cell type in the body from liver cells to kidney, muscle, and even brain cells. So, to me, this seems like a huge breakthrough and I'm quite shocked that more people aren't talking about this, and that people are still throwing the placenta away every day.

So, I've heard you say and I think I'll sort of quote here that, "Yes, there are stem cells there. Yes, they are viable. And yes, we can get them out." So, maybe we can start there.

Frans: Sure, we can start there. And not to correct you, but sickle cell and thal, both of them are genetic disorders and they can only be cured with stem cells. So, in other words, that led actually to me looking at the placenta as a source because we also developed in this institute the use of cord blood, sibling cord blood, to transplant individuals for leukemia or sickle cell disease or thalassemia.

And so, the reason that we started looking at the placenta is we started to look upstream because a cord blood unit that is used a lot currently in bone marrow transplant simply doesn't have enough stem cells to cure somebody like you or me. So, that's why we started looking at placenta...

Rhonda: An adult?

Frans: An adult, yeah. And so, obviously, in the pediatric institution, you're interested in transplanting kids. But for the adult population, you also would like to have a good source of stem cells. So, stem cells can, as you say, become any cell in your body including your blood cells. So, if you have a bone marrow transplant, what you do in order to cure cancer or cure a genetic disease, you need stem cells to do so.

Rhonda: Right. So, let me...

Frans: And so, that's where it comes from, okay?

Rhonda: So, let me ask you though. The difference between, for example, a cord blood, which I think a lot of the listeners are familiar with, the fact that you can actually bank and freeze your cord blood, is that these cord blood stem cells, they're mostly hematopoietic stem cells.

Frans: Yes, although, also, people also showed that they can differentiate into other kind of stem cells. But you know, one of the things that you have to keep in mind with all of this is that people have heard about embryonic stem cells, right? Because all of us start with one cell, okay? And that makes us, all right? So, everybody starts with one cell, you know, and that's how we start.

And so, nine months later, obviously, the baby is born. But during those nine months, that embryonic stem cell that starts at one cell becomes now trillions of cells, right? And part of that trillion is the baby. And part of the trillion is the placenta because they both grow at the same time, because the placenta is the interface between mom and the baby.

And so, after the baby is born, you can then consider to draw blood from the placenta because nobody is harmed, right? The baby is born. Mom will deliver the placenta. Normally, it goes into the bucket and it's just thrown out. So, that's where you get your cord blood, out of that placenta with the cord that is still attached, okay?

And so, it makes then sense to say, "Well, if you can get cord blood out of it and you throw away that big chunk of human tissue, which happens to be the placenta, is there nothing there to look at? And obviously, that's why we went upstream. We said, "Well, we have cord blood, but what's actually in the placenta?"

Because in contrast to embryonic stem cells, there is no ethical issue at all, one. Two is that if you want to have stem cells that will represent the genetic pool of the human race, it's a very good idea to just look at placenta because babies are born all the time. And whether you're in Japan or whether you're in Kazakhstan, or in Ireland, or wherever you are, babies are born, and that placenta from that baby, obviously, is the same as the genetic background of that particular population.

So, the whole idea with using placental-derived stem cells is that you have now a source of stem cells that is very cheap, very easy to get. You get trillions of them, so you don't have to do all kind of difficult things.

Rhonda: Trillions of them?

Frans: Oh, yeah, trillions of them.

Rhonda: Wow. So, how many...

Frans: So, it's a lot of cells.

Rhonda: Compared to cord blood...how many stem cells do you get from cord blood?

Frans: Well, I mean, you know, you have to keep in mind that these numbers look big, okay? But I can also tell you that if you take 1 microliter, which is, you know, 1 square millimeter of blood, it has about four million cells in it, okay? And you, as we sit here, we have in the order of, let's see, 10 to the 12th, which is a number that looks extremely big, right? But these are trillions of cells that we have in our body as blood. And we have trillions of cells in our body that makes us. So, these numbers look big, okay? And they are big.

Rhonda: But cord blood stem cells relative to placental stem cells, they're relative....

Frans: Oh, yeah, relative. I mean, cord blood...

Rhonda: How much more stem cells?

Frans: Well, let's look at this. Cord blood will be maybe 100 milliliters, which is about 3 ounces of blood, right? Now, a placenta is 1 kilogram. It's about 2 pounds of human tissue. So, in other words, if you simply compare that, then obviously, you get many, many more cells in the placenta than you have in cord blood. Okay? So it's just a rich resource and the big difference between embryonic-derived stem cells and the placenta is that it's very difficult to take one embryonic stem cell and grow it until you get trillions of cells because that embryonic stem cell doesn't stay a stem cell. It becomes different kind of cells, right?

On the other hand, if you take the placenta, and nature made that for you, and unless we are better in growing embryonic stem cells to trillions, we let just nature do its job, and they do a great job, and they've been doing that for millions of years. So, why don't we use it?

So, the whole argument with this one is that don't throw your placenta out. Let's see where we can use it. And yes, we have shown in 2009 the paper that you referred to, but we had another paper in 2012 that really shows that in the human term placenta, so this is the placenta that is normally thrown out, no problem with some people who wanna keep the placenta, but most people don't even see it. So, we say, "Well, keep it." And then, if you do that properly, you can tease out of those placentas cells that can become any kind of cell in your body. So, it can be...

Rhonda: Did you show that?

Frans: Yes, we have shown that. So, in other words, what you can do, you can take a placenta, snip it up, put it in cell culture, that's what you can do in the lab. And then, you can tell the cells, "Hey, I want you to become a neuron," or "Hey, I want you to become a fat cell," or whatever you want. And by feeding him certain kind of, you know, feeding medium, then they say, "Okay, fine. If you want me to do that, I'll do that." And then, you get cells like look like neurons or you get cells that look like heart cells, or whatever you have.

Rhonda: So, let me ask you...

Frans: So, that is that multipotency or pluripotency like you talked about. So, in other words, the pluripotent or multipotent essentially means that you have the potency, so you can, to become multi, so you can become anything. And so, the whole trick here is that if you do that properly, you can now get different kind of cells from placenta. And so, that also means that if you don't think where a placenta is coming from, then you can get different kind of cells with the genetic background from where the placenta came from.

So, in other words, you can then create cell lines, if you want to call it that way, or cell resources, if you wanna call it that way, that not only can become anything, but also will then have the genetic background such that it may fit whoever needs it. Okay? Because there are two options here, either you were born and you keep your placenta somehow for later use when you're 80 years old, you know, or whatever, or you have enough placenta stored in placenta banks that you just go there and find one that will fit you. So, there are two different ways that, you know, you can deal with that. And people, obviously, don't deal with that right now, but that's the future, and that's where we will go for it. Okay?

Rhonda: Can they? So, you mentioned that you have a...I think you have a patented procedure for saving the placenta, freezing it down so that you can later then grow that.

Frans: Yeah, we have that.

Rhonda: Now, is this something that's commercially available?

Frans: Not yet.

Rhonda: Not yet. So...

Frans: So, the whole thing with this one goes. First of all, you show the proof of principle in an academic setting like we are here, okay?

Rhonda: Mm-hmm.

Frans: And then, in order to bring it to the next step, sure you can start with a small company and you can say, "Hey, here. This is how to do it," right? I mean, you have a startup company. You say, "Well, this is how we're gonna do it." And so, that means that you then show, "Okay, if you do it this way or that way, or this way, or that way, then yes, you can store your placenta." And it's not that you can just put it in your freezer in the kitchen, okay? It's a little bit more complex. Because what you want to make sure is that what you put in your freezer also will be alive when you get it out of your freezer.

Right? So, you cannot just take your placenta after the baby is born and put it in your freezer in the kitchen and hope that it'll still be okay in 10 years from now. Ain't gonna work. So, you have to develop technologies, and that's what we have done, to put antifreeze in that placenta such that you can then put them into liquid nitrogen. So, in other words, it's not what you have in your kitchen. I mean, this is minus 100, 200 degrees centigrade, so very, very cold.

But if you do that properly, then those placentas that you then store in your liquid nitrogen can be pulled out later, thawed very carefully. And then, the cells that are in there say, "Okay, here we are," and then, you can put them into cell culture, and you can grow them. So, that process of going from collecting the placenta, freezing them, getting them out, teasing the cells out of the tissue, growing them in a way that they become whatever you want them to be, that is obviously a complex technical procedure. That is one, okay.

Now, we're good at that. We know how to do that. But now you get in how do you store that? Well, we are not going to store 100,000 placentas here, okay? We're not. But there may be companies that are interested in that. So, what we tried to do is convince people who currently collect cord blood and store that, or other people to, "Yes, hey, don't only store cord blood. Store the whole placenta. Don't throw it out." And that obviously doesn't necessarily mean that you have to store every placenta from every baby that is born.

So, what I said earlier, what you need to do is you have to see, "Okay, how many different kind of placentas do we need to store in order to have a match for you or for me, or whoever needs it. Okay?" That's one way of doing it. And the other option is, obviously, if you have a baby and you say, "Well, my baby is born and I wanna keep the placenta because when the baby is now 20 years old, he needs it." Well, you could do that, too, right? I mean, these are different kind of ways of doing that.

But currently, that was your question is, is it commercially available? Not yet. Will it be commercially available? Yes. When? I don't know. I hope next year. But it'll probably be made a couple of years from now. I mean, that takes time, you know.

Rhonda: Yes. Are you looking for some venture capital to...

Frans: Obviously, we do. I mean, obviously...

Rhonda: Okay. Well, I definitely hope someone steps up to the plate for that because it seems pretty important.

Frans: No, no, no. They should. I mean, the whole idea with this kind of...and it is not unique. I mean, it's the same, kind of, with a startup company in electronics or whatever you have. There's a lot of startup companies in biology that have...they think of these good ideas and I think, obviously, this is a great idea. But then, bring it into the commercial realm of things, that's a very different story because, obviously, I don't have the millions to develop it into a commercial product. But obviously, if people would help with that and partner with that, and obviously, that's what we currently are doing, looking for partners and some of them we have. And, you know, so, you have to build that toward something that then becomes commercial enterprise. And it can only become a commercial enterprise if people buy your product, right?

Rhonda: Exactly. So, I wanna step back, and it sounds like...I mean, this is, to me, is obvious. I mean, someone should definitely back this up, like, ASAP. I mean, I'd be doing it, you know.

Frans: Well, I mean, I agree with that, too. I mean...

Rhonda: But back to a little bit of the biology here. So, the ability to use these stem cells that are pluripotent, you know, from the placenta for therapeutic applications. For example, you mentioned cancer. I know that leukemias, a lot blood cancers, I mean, people that they undergo chemotherapy, radiation, they lose a lot of their immune cells and they end up having to wait for bone marrow transplants, which oftentimes, they can't find a recipient or a match. And so, you know, you've got, you know 50% of the time, people can't find someone to have their bone marrow donated. So, what sort of therapeutic applications are we talking about here with these stem cells that can be harvested from thing...you know, I think there's something like 3.8 or 3.9 million births just in the U.S. alone every year. I mean, that's almost four million placentas in the trash.

Frans: Yeah. I mean, do the numbers here, you know.

Rhonda: Right. So, what does this mean, you know, for...you know, you also mentioned cord blood. We know cord blood doesn't have nearly as many stem cells. It also can't form as many different types of cells. But there's a small amount of these cord blood cells that have been used to treat childhood leukemias, for example. So, what can these placental stem cells do in terms of the therapeutic...

Frans: Yeah. Okay. So, in other words, we open up a field which is currently, obviously, in development because you read in the papers all the time what you can do with stem cells and whatever. You know, there's a big promise there. The thing is, cord blood is a good example because it has been used and hundreds of kids have been cured with the use of cord blood. So, yes, those stem cells that form new blood because it replaces your bone marrow have been used and have been very successful.

There are obviously studies going on to see whether you can use stem cells for other reasons. Now, one thing to keep in mind as an example, if you cut yourself, right, then you have obviously blood is coming out and stuff. And then, it will be repaired because after a while, you know, you don't see them. I mean, you have maybe a scar there, but obviously, it is repaired. Now, that is because of the stem cells in your own skin that do that, right?

And so, that also means that what you can think about using those stem cells to not only repair that if you find a good match, you know, because you talked about a match. In the bone marrow, you need a good match. Otherwise, your body will recognize the new cells as not good or the other way around, the new cells that come in recognize you as not good, and that's not matching. That is not good at all. I mean that's very, very bad. So that's...

Rhonda: So, basically, the immune system is going to attack.

Frans: The immune system...yeah. I mean, that's what immune systems should do. I mean, they have to recognize something that is not you and they have to kill it, right? Or the other way around, if you get new immune cells, they will recognize you as, "Hey, I don't recognize you. I'm gonna attack you." And it's called graph-versus-host disease.

So, that's when you talk about good matching. And that matching means that the stem cells that you then give to individual should really fit. And that's also what I said. If you look for the genetic pools that you look at, you have to look for the fits, right? And so, if you store enough placentas or enough cord blood or stem cells in general that would fit anybody in this planet or the better part of that, then you're pretty good.

Now, where could you use it for? That was your question. Bone marrow transplant, obviously. But you have to think about anything that needs to replace something in your body that doesn't work properly anymore. And obviously, if you get older, you know, you get many more problems like that, right? But in principle, every cell in your body has the same DNA, all of them. So, you have to wonder why my finger looks different than my nose. Well, because there's a program that tells, "Hey, I mean, I wanna be a finger and I wanna be a nose." But it actually means that every cell, in principle, can either become a finger or a nose, right?

So, that also means that if you now provide stem cells that will become new heart tissue, well, you could use it to repair somebody who has a damaged heart after, you know, a heart infarct, for instance. You could also use stem cells to replace cells in your eye because, for whatever reason, your eyes don't work properly. You could use stem cells because you, by working in the sun your whole life, you get patches of your skin that are not good anymore, you know, and they will have to be removed. Now, that means that your skin either has to do it himself or you can give stem cells to give you a new nose or whatever you want.

So, it is obviously a little bit science fiction because, obviously, we are not able to do it right now. But that's where it will go. So, in the next decades, what we'll see is that these pluripotent stem cells, stem cells that are able to become any tissue, will now become a tool in the toolbox of a physician to repair whatever needs to be repaired. Okay?

So, it's not happening tomorrow. Part of that is already in place like bone marrow transplant, you know. Part of it may already work to help to repair burn victims with repairing, you know, whatever they have damaged on their skin. So, there are all kind of things that are currently are happening and it goes really into that direction. So, these multipotent or pluripotent stem cells really are the future of tissue repair if you wanna call it like that.

Rhonda: Yeah. So, I mean, I know that they're doing a lot of work now in this regenerative medicine field with induced pluripotent stem cells, where they're taking skin cells and they're...you mentioned this generic program where they're throwing in some of these gene factors, that can say to the skin cell, "Hey, I want you to become a stem cell. And then, once you're a stem cell, then I'm gonna decide what other cell type you're gonna become."

And, you know, there's a lot of promise in this field because they're now able to basically take just a skin cell which we are sloughing off every day and make them into these pluripotent stem cells. And there's been a lot of work in animal models where they've now been able to regenerate, you know, neurons, lost neurons, or spinal cord...

Frans: Well, yeah. But I mean, as you know, we are not smart enough as humans, currently, to make these IPSC, induced pluripotent stem cells, in a way that, yes...because, what I just said before, this becomes a finger, this becomes a nose. So, somehow you tell the cell what to do, right? So, you can actually say, "Okay, guys, why don't you go back in your development like a skin cell? You're not a skin cell anymore. We make you now back into a stem cell."

Doing that, obviously, needs to be done by pretty harsh treatment. And as a result of it, you can end up with cells that are not necessarily...I mean, I don't wanna use as a human those cells, okay? I mean, you can do some kind of study. I mean, obviously, these studies are done. But we, by far, are not ready to use that for a human being because you really...

Rhonda: But we have.

Frans: You really have to be very, very careful with that. Because what you do by modulating cells, you know, and bringing them back to be more primitive, you turn on genes that also mean that, yes, they grow now, and uncontrolled growth has also another name. It's called cancer. Okay? So, in other words, if you are not very, very smart in telling the cell what to do, the cell will take on its own life, keeps on growing, and that's what you call a tumor. So, you have to be very, very careful. That's one.

And two, you can also ask yourself, "Well, do I wanna take a cell from my skin which definitely has been along for 60 years, right?" And it is not necessary as good anymore as the teenager, which I call the stem cells that I have, that are only nine months old because, obviously, during life, you know, as we live, aging happens. Aging happens to the individual. Aging happens to the cells. And so, that means, in time, your cells get older and older and older and older. And you can see that if you look at an individual, you look different. I mean, you're 80 years old or maybe you're 20 years old, right?

And so, that means that all the cells getting older. So, then you can ask yourself, "Well, sure, I can reprogram it to become something else by taking a skin cell from a 60-year-old. But hey, you still have a cell that happens to be around already for 60 years." And there's nothing you can do about that because that's how you start. You cannot just take time back, okay? There's no way.

So, there are arguments to be made that even if we would be very, very smart and being able to really do a very good job in using those IPS cells, you still end up with cells that you start off with that are pretty old. That's one.

Two, is that if you have an IPS cell, they still have to grow into a cell line, and you start with a couple of cells. How do you get trillions of cells? You have to grow them. And in order to grow them to become of therapeutic use, you have to have a lot of cells. And then, the problem is it's not only that you have to be smart how to program them to become whatever, but then you still have to grow them, you know. And cells have the tendency of differentiating, becoming a little bit different because they will talk to each other, okay?

So, that's how we start as a human being. You start with one cell. Now, look at me. I mean, I don't look...my cells look different. And the reason for this is all those cells talk to each other, and that happens in cell culture, too. So, that means it is very difficult to keep all those cells exactly the same, you know, in order to use it for therapeutic use. So, obviously, I'm talking about where would you get them. And I will say, "Well, you know, if you're smart enough to get young cells from a placenta and you have tons of them, hey, it's not bad."

So, I'm not saying that IPS are not good. I just say IPS or embryonic stem cells, or placental cells, or cord blood cells, they're all different resources that you may use for whatever you want to use it for. And it's not that one kind will take over everything then the others are not good. This is just another resource which I think is a wonderful resource that we shouldn't throw out.

Rhonda: I agree. And you mentioned something on your first point you were making about the IPS cells, how they're aged, they're older. And there's, you know, been a whole slew of publications that have been looking at the epigenetic marks on cells as they age. And there's a complete program, an epigenetic program. So, epigenetic means these are not changes in the DNA sequence itself, but they're these factors that'll sit on top of your DNA, so to speak. And they can turn genes on so the genes are doing what they're supposed to do, or they can turn genes off, so genes, even though they're there, aren't doing necessarily what they're supposed to do.

But what they found is that there's an epigenetic program that happens with aging. And you can compare...and they've done this in people. They've taken blood cells, from young individuals and old, you know, different ages, and they've seen there's patterns, methylation patterns, for example. And they can take a blood cell from a person and guess their age, and they get within five years, plus or minus, which is quite striking to me.

So, it'd be interesting, you know, one, with these induced pluripotent stem cells, you're right. If you get them from an older person, this is an aged cell, it has a different epigenetic...

Frans: Yeah. And can you put that epigenetic program back, right?

Rhonda: Can you? That's the question.

Frans: Well, that is currently...I mean, that's what I'm saying. We're not there. But ultimately, we may be smart enough to take a cell from me as a 60-year-old and say, "Okay. We're going to modify you not only to become anything that we want, but also turn back time and the epigenetic program or whatever you have there, modify everything, go back, and be smart enough that you end up with a cell that looks like I would look when I was born, all right?" Now, if we are there, then yeah, that would be wonderful. And then, we can start again. But we're not there yet.

Rhonda: You're right.

Frans: So, in other words, yes. I mean, there's a lot of promise. There's a lot of promise in these different resources. And obviously, where we are now is completely different than we were a decade ago because we wouldn't even have thought about this, okay? So, yes, I mean, things are developing very rapidly. And I will be the last one to predict where we will be in 10 years from now because, I mean, they are probably things happening that I didn't even think of, okay?

But what I'm saying currently, today, as we are, we have good resources, cord blood, to replace bone marrow in kids that need it, with leukemia or whatever. Yes, we are developing another resource coming from the same kind of angle, which is the placenta. And yes, that will be a resource that can be used. And at the same time, yes, sure, we should keep on working on embryonic stem cells and see how we can be smarter to understand these patterns of epigenetics and whatever you have. Yes, we should try to make smarter protocols and better recipes to make IPS cells such that they become anything and turn them back in time. Those kinds of things all happen at the same time.

And so, it just depends what you wanna do. And so, the only point that I wanna make is that, yes, we have a resource that nature provides us. Use it. I mean, that's essentially what what I wanna say. And so, yes, we may be smarter than nature at a certain point to doing certain things. But at this point, why don't we use it?

Rhonda: I agree with you. I...

Frans: I mean, so it is not a competition between IPS and embryonic, and whatever. All of them will happen at the same time and you pick what you need and you do what you need and, you know, and that's how that goes, right? So, that's the way I see it.

Rhonda: Yes, exactly. I think something with the placental stem cells that also is very interesting is the ability to be able to form neurons, you know. And so, if you think about it in the context of neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, this could be a game changer. I mean, people are out there researching, trying to find a cure, you know, trying to find, obviously, ways that you can delay, you know, these age-related diseases that also very important. But to me, it seems as though being able to make neuronal stem cells, you know, for the hippocampus, substantia nigra, you know, all these different brain regions, I mean, brain atrophy happens with age. It happens accelerated...

Frans: Where are my glasses? I mean...

Rhonda: Exactly. So, the fact that these placental stem cells you said can form neurons as well. And so to me, it seems like why wouldn't we start using this rich source that we have to start forming neurons and doing these studies where we can say, "Okay. Can we replace damaged neurons, you know, first, obviously, in mice, but also, ultimately, in humans?" You know, have you been able to show that a placental stem cell can form a neuron? Has that been shown by you or others? Are you aware?

Frans: Well, we have and I can...I don't know I have it on my wall. But otherwise, you can look in the paper that I published. We have shown that.

Rhonda: You have shown that?

Frans: So, we have shown that. So, they can become neurons. They become any cell that you want in a sense, right? Because you're able to teach them not whether they will be a functional brain cell, that's a different story, okay? Because if you show that cells get the characteristics of neurons in a petri dish like you do in stem cell lab, it does not necessarily means that I can suddenly replace somebody's brain cell, okay? That's another step, all right?

So, another thing that I wanna mention to you is what is important to keep in mind if you talk about stem cells and regenerative medicine. One of the things is that you have to think about is that cells are never living by themselves. They live in a community. It's like a village. If you're go into a village and you wanna buy a sandwich, right, you need a whole bunch of different folks to work for you. You need somebody who, you know, grows the corn that has to go to the bakery who makes whatever, and then you need, you know, the butcher who gives you whatever, the ham that you wanna have and you get another for. And you know, etc., etc.

So, it's like a village, you know. So, that means that cells talk to each other like in the village, "Hey, I wanna have this, I wanna have that." So, the way that cells talk to each other, they don't get on the phone, all right? They don't have that. But they use chemicals that they generate, spit out, and then the guy next door says, "Oh, that's what you want." And then, that guy will spit out another chemical that goes to another guy, "Oh, that's what you want," and ultimately, you end up with a community of cells that, together, become whatever you need to be. It's the same thing as in the village and buying your sandwich. But it means that it's not only the cells that are important. It is also the chemicals that they spit out that are important. These are the signals that, like, you do whatever.

So, you have to think about if you have a damaged tissue, you cut yourself. So, what does that mean? Well, that mean, obviously, cells are screaming murder because, I mean, something happened to them. So, they send out signals. "Hey, we need to do something." They send signals to other cells, "We need to do something." And before you know, you know, it starts to grow and you repair your tissue, okay?

So, then you have to think about, "Okay. How could I use young cells like from placenta to help with that? Do I need the cells to replace the damaged cells or do I simply need cells that help with this whole process of talking to each other?" And so, one of the things you can think of, and that has nothing to do with matching now because, I mean, you know, that is the kind of stuff that I'm also developing, which is very different, is that you say, "Well, you can have a biogenerator which, essentially, is just a tube with cells in it, okay?" And you let them talk to damaged tissue, which are the signals that come out. Those signals now come to those stem cells, say, "We need to do something." And they start to make growth factors and they're gonna start to make order, and that comes out on the other end. And that goes back to your damaged heart or liver, or whatever you have. And that will then help the liver to regenerate better.

And that's the kind of stuff that I'm thinking about doing now with pediatric liver transplant using UCSF as an example. You say, "Well, it's not necessarily that you have to replace those cells, but maybe the cells that I have can help to generate an environment that that liver that was damaged and was taken out from that baby is now being able to grow better because of help, you know."

So, in other words, it is a lot more complex story than just talking about a cell replacing a cell. It is also thinking about the cell population that talks to other guys and generates chemicals, growth factors, and cytokines, and whatever you wanna call them. And these chemicals help tissue to regenerate. So, that means regenerative medicine is more than just replacing cells. I mean, there are many more things that go along with that.

So, if you talk about an IPS cell or an embryonic stem cell, yes. I mean, you can talk about that cell that can then grow there. But you could also think about, "Well, maybe I should use those cells to generate growth factors, to help you and me to have my nose repaired a little bit faster, okay?"

Rhonda: I'm so glad you pointed this out because it reminds me of recent headlines where Amy Wagers who went at Harvard and some others found that when they transplant, for example, blood from young mice into old mice, something happens that are able to regenerate liver, heart...

Frans: Yeah. That it is a...

Rhonda: It was a growth factor.

Frans: That is exactly what I was going at. So, in other words, it does not...because you really have to think about if you have...and that's also coming with the age of cells comes back. If you have these nine-month-old cells, you know, they have been developed over the last nine months into the placenta and the baby. So, they are vigorously making anything that that fetus needed to become a baby, all right, or the placenta to grow itself. So, these are cells that are really programmed to make growth factors into anything they want at a high rate. So, why don't we use them?

Rhonda: Yes. And so, these placenta cells are making growth factors?

Frans: Yeah.

Rhonda: There's also, you know, stem cells can replace damaged organelles in other cells like mitochondria. So, you know, these placental stem cells are, like you said, nine months old. They're young. Their mitochondria are healthy. So, not only can we replace the damaged cells, you know, damaged muscle, liver, possibly brain, but we could also potentially have different growth factors that these placental stem cells are secreting.

Frans: You use them as bioreactors. That's what you do. Because, I mean, if you look at the soup, let's call it a soup that they make, there are hundreds or thousands of factors in there, right? There are some of them that are a lot. Some of them are very little. But again, I mean, it's like cooking. I mean, that one little ingredient which is only a very little bit makes the difference whether it tastes good, yes or no, okay?

So, it's the same thing that the cells make. They make this big mixture of chemicals that help to grow stuff like you indicated in these mice. But you need all these little things in the right amount. Otherwise, it doesn't taste good. So, it's very, very difficult for us. I mean, sure, we can use all kind of technology to take the soup and analyze it, and say, "Well, we got 99% of this and 1% of that," and whatever you have, right? But ultimately, the complete recipe that the cells make as the result of a screaming kind of, "Hey, we need something," right, that is what is needed. It's very difficult for us to really make that.

So, my argument is, well, don't try to reinvent the wheel, you know. Use the cells to let them make what they are told by other cells to make, and let's use it, right? Because it will be very difficult. And that's what you've seen in studies like you mentioned. We find very, very interesting data by this concept, you know, that cells can help, can do things in order to make other things work, right? And so, yes, that's another part of regenerative medicine that we should not forget, okay? So, it's not necessarily only the cells that now become another cell. It is also the cell that can do things that the other cells need, right? And so...

Rhonda: And supply these factors to make those cells do things that they're not doing because they're old.

Frans: Right. And so, in other words, yes, I mean, they try to. But, you know, obviously, as you mentioned, I mean, the epigenetic reprogramming that happens over time makes them, "Yeah. Maybe we're a little bit not able to make those growth factors anymore. What do you want?" So, in other words, why don't we give to the other cells that can do it, right?

Rhonda: Yeah. You mentioned this thing of having this placental stem cell bank, so to speak, almost like...I mean, we've got blood banks now, where people donate blood and they, you know, they bank it. And, you know, I was thinking, for me, you know, well, I haven't had a child yet and well, you know, when I do have a child, if that placenta which is obviously...the stem cells in the placenta are from the fetus, right so they're technically...

Frans: Well, I mean, they're both. I mean, you know, you'd have to think about they're both just coming from this one cell, which is, you know, when you get this one egg cell, get sperm, boom. Here we go. That's it. That's the one that's the ultimate embryonic stem cell. You start at one cell. And that one cell, obviously, in time, becomes a lot of cells, and part of these cells become your placenta and part of these cells become your fetus. And that keeps on going. And in the end, if you end up with a baby and you end up with a term placenta. So, in a sense, both of them are made by the same starting material.

Now, the placenta's a little bit more complex because part of it is mom and part of it is baby, right? Because that is the interface, you know, how the baby gets oxygen and nutrients from mom, right? But after the delivery, yeah, you can tease it out and you can take the baby's part. And then, you know, you can get your cells that you want.

Now, should we bank it? Should you bank it? Well, as you probably know, is there are, I don't know, 250, 300 cord blood blanks on the planet currently, and these are banks that store cord blood.

Rhonda: Yes, I do know that.

Frans: And so, these cord blood banks have different...there are two different attitudes. One is that there are banks that are called private cord blood banks. So, that means that if you are ready to deliver a baby, they can collect that cord blood and put it in a bag and store it for you. The other opportunity is that you'll say, "Well, I don't care. I want to store it for anybody who wants to use it." And that's called the public cord blood bank. So, in other words, they don't store it for you, but they still store it for anybody who needs it, okay? These are the two different types of cord blood banks that currently exist, all right? And both of them are aimed for the same thing, those cells in cord blood could be used to transplant if somebody needs a bone marrow transplant.

Now, you can take the same kind of system and say, "Well, we're not only going to collect cord blood, we're also going to collect the placenta." Why not? And so, we developed a technology that, yeah, if you put antifreeze in it, you could put the whole placenta in the freezer. Or what you could do, that's another that we have developed, we can pull cells out and make a second bag, and put the bag into the freezer. I mean, there are different ways of doing that. But the bottom line is, there is a resource that is currently going to biological waste that I say, "Well, don't do that. Store it." Store it as a placenta as a whole. Store it as a bag where you get part of it out."

I mean, there are all kind of different ways of doing that. And I think ultimately, it will come to the fact that at least part of, maybe all of the cord blood banks, as an example, will say, "Okay. We can store your cord blood. We can also store your placenta. Do you want that, yes or no?" Or for a public bank, they can say, "Well, we're going to store cord blood and the placenta because you never know, somebody may need it," right?

And so that is where it will go in the next decade. And there will be people, you know, who think that it makes sense from a public health point of view to store them or for themselves to store it. Or, I mean, there are different kind of scenarios, but it comes down to the same thing. Don't throw away your placenta. Keep it.

Rhonda: All of the above. I think, you know, I recently banked my wisdom teeth because...

Frans: Oh, you did? Oh, I didn't.

Rhonda: Yes, I did because I had to get them removed. They were impacted. I don't recommend...if you don't have to get removed, it's really traumatic, so I wouldn't recommend it. But if you do, there's dental pulp in the wisdom teeth that also has stem cells, which are mesenchymal, so they can form cells that are, like, of the cartilage bone and also, you know, other tissue types that are relatives of neurons. Not quite neurons, but they're getting there.

So, the fact that they are banking these, you know, my dental pulp from my teeth and not the placenta, to me, is just absurd. And I'm actually a little frustrated right now because I feel like there's so much possibilities with these placental stem cells that, I mean, even while we're teasing out all the little details about can a neuron be functional and things like that, we should be freezing this down. We should be doing that.

Frans: It's all a commercial issue.

Rhonda: So, it's all a commercial issue.

Frans: It's all a commercial issue because you have to look at it. I mean, we have currently the ability to do it, okay? So, in other words, if I would get now a placenta tomorrow, in principle, I could take a placenta, use my technology, put it into liquid nitrogen, and store it. Okay? But doing that will cost money because I have to get it. I have to do something with it. There's time and effort and materials involved. And then I have to put it into liquid nitrogen. Well, then I have something that I put in the freezer. Now, that freezer needs liquid nitrogen, costs money. The freezer needs to get new liquid nitrogen every week.

Rhonda: But they're freezing cord blood. They're freezing...

Frans: I understand that.

Rhonda: They're freezing dental pulps stem cells.

Frans: Yeah. You don't have to convince me, okay? So, but the point is I understand that you have to then have people who think, "Yes, we should do that right now." I agree with you, okay? So, who would do that? Well, go ahead. Set up a company and let's do it, you know. Let's put the money there. And, obviously, yeah...

Rhonda: Okay. So, you have a company. What's the name of this company called?

Frans: Well, it's very classical. It's called Plasalus.

Rhonda: Plasalus.

Frans: And where is it coming from?

Rhonda: Can you spell that?

Frans: P-L-A-S-A-L-U-S. And the reason for that name is, "pla" is from placenta, which is the Latin word for the cake-form organ that the placenta is. And then, I thought, "Well, you know, we use placenta for health. Why don't we use the Latin word for health, which is 'salus,' S-A-L-U-S?" So that's where the name came from, Plasalus.

Rhonda: So, what can this company...

Frans: And so, what we do as a company, we provide the technology that allows you to deal with the placenta in the ways that we talked about. So, we provide the knowledge to know how to take a placenta, do whatever what you wanna do in order to get hematopoietic stem cells out of there, do whatever you need to do in order to get cells out of there that can become pluripotent or multipotent cells, do whatever you need to do in order to take the placenta, freeze the whole placenta. We developed the technology. We provide the technology, all right?

And so, that is the whole basis for that company. But you have to realize, this is a startup. So, we have two directors, two janitors, and they're all the same people. So, my colleague and my...so, Vladimir Serikov, you know, obviously, is not here today. But Vladimir Serikov and me, we are the directors, the janitors, and whatever of that company, okay? So, that's what we do. And we formed that company simply to take our technology, which we have proven now in an academic sense, and try to commercialize that, all right?

And so, that means that then gives you the opportunity to talk to corporate banks or whatever you have and say, "Well, guys, we feel that it is a great idea. Go for it." And then, it depends a little bit who wants to put money on the table and how that goes in order to start that because no matter how you look at it, it's a great idea what you said, "Take a placenta. Store it right now." I agree with that. But what you need for that is somebody who takes it and stores it. And you need storage facility and you need a building that it goes in. I mean, and before, you know, we talk about a lot of money. But that kind of investment needs to be done, needs to come, and it will come if there is a feel for commercial viability. Because in our country, if you don't make money out of it, it won't happen, okay? Most of the time.

And so, that then gets into why would you store placenta, as well, for medical use? Well, you know also how the whole medical insurance system and whatever we have in the U.S. is pretty complex. Put it this way, okay? So, that all goes into the same thing, where is the money coming from? Because it's wonderful to store your placenta, but who's going to store it, for what? And who's going to pay for it? Because that's the question that you get, right?

Rhonda: Well, the consumer.

Frans: Yeah, the consumer.

Rhonda: The consumer can pay for it. You know, right now, I paid $625 to get the whole process done, you know. And now, I pay $125 a year to have them stored in liquid nitrogen.

Frans: And that is exactly what they do with cord blood. Because there is your private cord blood bank. That is one of them that I just talked about that is, "Can we collect your cord blood?" "Yes." "You wanna pay for it?" "Yes." "You wanna store it?" "Yes." "Okay. You get a bill every year and we store it for you."

Rhonda: And consumers are interested in doing that. You know, if...

Frans: And that is if you get a company who says, "Well, we don't only wanna, you know, store cord blood or your dental stem cells. We also wanna store placentas because we've got enough people who are interested in doing that," whoop, it will take off, okay?

Rhonda: Well, I'm gonna be advocating this placental stem cell because, I mean, this needs to happen. And if you're just looking for someone to license the technology, some venture capital to back this up, I really, really, really hope that someone steps up to the plate and does that because, well, for selfish reasons, I wanna freeze my, you know, future placenta.

Frans: Right, right. So, you need somebody to offer you that opportunity.

Rhonda: Yeah, and also other people's placentas. Like you said, if we can...

Frans: Because that is the other part, right? I mean, the private one is your placenta, and that is really you want to do it for yourself. And it's fine. But there's another part to it, is that, well, maybe we as a society, however we wanna pay for it, it's the same thing as medical insurance, right How do we wanna pay for somebody who needs it tomorrow? Because what you mentioned earlier on, thousands of people die every year because they do not have a proper resource for their bone marrow transplant or whatever they need. Thousands of them, all right? And so, that means that those people, if they would have that resource, would not die, and that we as a society would be able to provide that to those people.

And they pay themselves. They're part of that society, too, because that's what medical insurance is, right? You pay not only for yourself. You also pay for somebody else. But if you need it, "Hey, there's money for you to be treated." So, that's the same kind of thing. So, that takes it out of you storing it for yourself and paying. It is more like, you know, how...and so, you see obviously then, that becomes a much more complex story, how do we as a society take care of ourselves?

Rhonda: But we should.

Frans: I do agree with that.

Rhonda: I think, just talking about the U.S. alone, with four million placentas every year, you know, you're talking about the possibility of extending the human lifespan dramatically. Because neurodegenerative diseases, heart attacks, infarctions, liver disease, lung cancer, you know, leukemia, I mean, we're talking about tuning up humans every so often, giving them these growth factors they need, possibly replacing some cells that are lost, and extending the lifespan. So...

Frans: No, I do agree with you completely.

Rhonda: I mean I have the vision. I can see it.

Frans: Yeah, I know. I have that vision, too. And it's just a matter of getting it to the next step, all right?

Rhonda: Well, the future looks really bright.

Frans: And the future looks bright.

Rhonda: And your research, thanks to your research, that has made it brighter. So, I thank you for that. And I really hope that...is it...can you say it again?

Frans: Plasalus.

Rhonda: Plasalus. So, is there a website if people are interested in going to...

Frans: Oh, we do have that. It's called plasalus.com. It's very...

Rhonda: Plasalus.com, so...

Frans: I don't know whether I have it on my screen. Oh, here we go.

Rhonda: Okay. So, you've got your...

Frans: Here we go. This is my website, very simple website, Plasalus, Placental Stem Cells for Health.

Rhonda: So, www.plasalus.com.

Frans: That's right.

Rhonda: And that's where we can find...

Frans: And so they can find me, you know. I mean, you can find me also here. They can find that stuff, okay?

Rhonda: Your technology is great.

Frans: But you know, the whole idea is don't throw it out. Use it.

Rhonda: Yes, please. So, we need to get this into the consumer world.

Frans: We need to get this to the next...yes. And that's what we're working on very hard, you know. We have some leads.

Rhonda: Well, thank you.

Frans: And anybody who listens to this who is interested, give me a call.

Rhonda: Yeah. If I ever make, you know, enough money to be able to back this up, I definitely will.

Frans: Right. I mean, if I would have the money, I would start it already or, I mean, I would have already started. So, unfortunately, in a lot of medical research, what we do in this building, what Bruce Ames is working on, or what I'm working on, you know, it really is the academic part of the story where you try to develop new technology, new things that will ultimately pay off. And you publish papers, and you do your stuff, and you have great ideas. But then, take it to the next step, yeah, that takes time. I mean, because obviously, there are all kind of things, you know. It's how do you store it, you have to get FDA approval, and you know, all that whole mix to go from a great idea that can be shown in the lab to something that will be of use to the general public is a big step.

Rhonda: Yeah, often decades.

Frans: Yes. And I think that, you know, unfortunately, you know, in the United States, and I will say it lightly, not the best at funding research, in general, over the last decades. It's going down all the time.

Rhonda: Particularly creative research.

Frans: And the problem with that one is that new ideas, and it's not my idea, it's everybody's good idea, do not get developed in a way they should actually, as a society like we are, because we have much more potential than we're actually banking on currently. And so, the National Institute of Health, as an example, has been retracting over time continuously.

And so, at the same time that we want to have better options to extend your life, to improve the quality of life because that's actually much more important. So, improving your quality of life for our population or the population in the world, in a sense, stands on research that is done in basic research, translational research, clinical research, and that kind of research needs money to be done. And so, it would behoove the Congress to put more money towards that because that will improve the quality of our population.

And then, the next step, obviously, if you have good ideas, how to get it into practice. That also needs funding. And if we as a society feel that it is beneficial, not only you and me but in general, then yes, that can be done. And that's what we have to step up the plate, you know. That's what we need to do.

Rhonda: Yeah. I agree, you know. And sometimes, relying on the government isn't...I think we're now moving into an era where we're able to get information to the people, and people themselves are passionate about, you know, wanting to improve the quality of their lives, and they're saying, "Hey, I wanna fund this." And so now, you just start to skip the government and say, "Well, NIH..."

Frans: Go crowdfunding.

Rhonda: You know, crowdfunding. You know, that's becoming more and more of an option where now it's like people are saying, "Hey, I've got some money. I wanna fund your great idea. I wanna fund this possibility of having placental stem cells frozen down and banks that we can later use them at the individual level and also at more of the societal level. So, that's another...

Frans: They're different approaches. They ultimately come down via different roads into the same thing. Crowdfunding, you pay directly. You can also pay your taxes, and then it comes in that direction. I mean, sure, we won't make this a political talk because we're not here for that at all. But, you know, all of those things come from a similar angle and different countries, different societies have different angles on doing that, you know. There are countries that do this differently than what we do and up.

But the bottom line is that if you wanna improve health, you really have to do the basic research and get it into the clinic. And how to do that, that's a challenge. And so, in a sense, we complain about the fact that we cannot store placentas right away. But the other thing that I must say is I'd also do a fair amount of work with parts of the world where this is a luxury to even talk about. If you go to the African continent, as an example, people die every day, thousands, hundreds of thousands of them with things that can very easily be altered, very easily.

And so, what is always frustrating to me, if you work in healthcare research and you have very simple things that can be done that are simply not done for whatever reason that would really improve the quality of life of that part of the population. And you know, when I was in Benin, you know, what was it, two years ago or something like that, you really go there and you work with those people. And you look at what they do and then you wonder, "Oh, we are very lucky where we live," you know. And it is really devastating to see kids die for reasons that are absolutely unnecessary and will not happen here in Oakland, in the Bay Area, absolutely not. You don't even think about it, you know.

Rhonda: Such as nutrient deficiency, viruses...

Frans: Anything. I mean, you can go anything. I mean, it may be that they're not vaccinated against whatever kind of disease. But they don't have clean water. I mean, you know, you can name it. I mean, so it's amazing. And what we currently then hear about the whole Ebola issue in Africa, right, you have to wonder why the few people who came over here, you know, survived and did well while most of the people in Sierra Leone or whatever it is just die.

Rhonda: Right, difference in care, healthcare.

Frans: Just difference in care. And one of the things that they figured out now in Liberia, as an example...and we talk about something that has nothing to do with stem cells. But what they found out, if you are able to give proper nutrition, proper care to a patient infected with Ebola, the chances of surviving really shoot up.

Rhonda: By how much?

Frans: Significant. I mean, you know, you cannot really say how much because you have to do it now. But this is more anecdotal, but it really shows that if you're able to take care of somebody, you know, in a very simple, basic way, you know, suddenly, it becomes life or death. And so, what I'm saying is that what we are complaining about with our placental cells, I always try to put it a little bit back in the bigger perspective what we as a human race do. And I think, yes, we should do that. And yes, this is just one other example, is that we have resources that we can use for the betterment of the quality of life not only for us, but for everybody. Because for the same token that we could use it, we could use it for anybody on this planet, you know.

Rhonda: Right. Yeah. So...

Frans: So, we have to keep that in mind, you know. It's...

Rhonda: No, it's very important how fortunate we are to be able to be here researching, you know, regenerative medicine and...

Frans: I feel very privileged that I have the opportunity to do this kind of stuff. And as the opportunity given to me that, yes, I will be able to do my little things and have fun with it, but at the same time, create something that may be good for people and may be helping. But it's really a privilege doing that. And I keep that always in mind. I mean, when I wake up in the morning and I come whatever kind of wild idea and can bring that into practice, that's wonderful, right? And I feel privileged doing that.

Rhonda: It's a great mindset to have.

Frans: Anyway.

Rhonda: Thank you so much, Frans.

Frans: You're more than welcome.

Rhonda: I really enjoyed the discussion.

Frans: Okay.

Rhonda: I'll catch you guys next time.