Victoria Maizes: Hi Andy.

Andrew Weil: Hi Victoria!

Victoria Maizes: Today we are going to be speaking with a stem cell expert and researcher, Dr. Doris Taylor.

Andrew Weil: I've been looking forward to this one. You know she is an expert in the field of regenerative medicine which I have long seen as the future of medicine.

Victoria Maizes: And I think it's fascinating, because one of the things you are so well known for is talking about the innate capacity of the body to heal, and it might be that stem cells are a very important underlying mechanism for.

Andrew Weil: I think it is probably the mechanism, and I can't wait to hear what she has to say.

Victoria Maizes: Fabulous. Let's get her on.

Victoria Maizes: Dr. Doris Taylor bioengineered the first beating human heart and is considered a global thought leader in regenerative medicine. She transformed the field of organ transplantation in 2,008 by developing a method that makes scaffolds for organs.

This achievement was recognized as one of the top 10 research advances by the American Heart Association, and Doris was nominated as one of the 100 most influential people in the world. By Time Magazine. Her motto is, “Build the future today and do it with heart”.

So welcome, Doris, for a conversation about stem cells.

Doris Taylor: Thank you. I'm thrilled to be here.

Victoria Maizes: We're delighted you're here, and I thought we would begin by asking you to define stem cells and regenerative medicine, because there is a lot of misconceptions about both

Doris Taylor: Sure. Let me start with the fact that stem cells are simply cells that can do 2 things. They can make more of themselves, self-renew, and they also can differentiate, become different kinds of cells. Virtually every organ or tissue in our body has stem cells. Stem cells are really nature's tool for what I call endogenous repair, self-repair. So regenerative medicine is the idea that we can treat an underlying injury rather than the symptoms of that injury that we can actually get to the root cause, fix that, and restore the body's capacity for endogenous or self-repair.

Andrew Weil: If stem cells are everywhere, if they're in all tissues, why doesn't self-repair happen more often?

Doris Taylor: Perfect question. I would argue that for a lot of our lives. It does. If you think about it when you fall down and you scrape your knee. This is a classic example I use. Fall down. You scrape your knee, turns red and then that is inflammation.

Inflammation is nature's cue that says “Help, I've got an injury. Send me cells.” and the cells move in. So if you're 2 years old those cells move in your knee scabs, it gets well, and you don't have a scar for the rest of your life.

If you're 62 or 72 fall down, scrape your knee, same redness, same scar, same quote repair. Except now, you're probably going to have a scar. Why? Because, as we age and based on the number of hits we take the number of stem cells we have go down, and the potency of the cells we have go down. So it's actually this balance and part of regenerative medicine's goal is to restore those cells and the potency of those cells, and I think of it in the context of heart disease. But it applies to everything.

Andrew Weil: I've always seen that as the future of medicine. But let me ask you what happens in the heart? Why, when a portion of heart muscle dies. Does regeneration tend not to happen?

Doris Taylor: Again. Great question. Two reasons. One. the time that regenerative medicine, intrinsic, endogenous repair fails is either when you don't have enough cells or you don't have enough time. in the case of the heart and I would argue the brain. Both are true. When you have an injury to the heart. A heart attack, for example. First of all, the blood vessel gets clogged and what happens is everything downstream that doesn't get oxygen actually can die if it's not fed for a period of time, right? So there is an inflammatory response. But there's no real capacity for cells to get to that region to actually mediate the repair. That's part of it, because the vessels are clogged. Number 2 in our heart and in our brain we have fewer stem cells than in virtually any other organ or tissue, and my worldview is because those are the 2 organs that are geometrically constrained.

The shape of the heart is exquisitely designed to pump. And if we had too many cells or cells could overgrow then it couldn't pump in the correct way, and that's not compatible with life. Same thing in the brain. It's a geometrically constrained organ. If you have too many cells, you get growth that is incompatible with life.

Andrew Weil: Too bad. That seems like a design flaw.

Victoria Maizes: Yeah, Andy, you know, when I listen to Doris, I hear you talking about the innate healing properties of the human organism. Can you say more about that?

Andrew Weil: I've always said. I think that's the most interesting aspect of our biology is that there is this intrinsic capacity for repair, for regeneration, for adaptation to injury and loss. And I think I've always seen my mission as trying to get build more confidence in people about that you know, most patients that I work with really don't realize this great resource that they have within.

Victoria Maizes: So I think of stem cells as pluripotential. You're sort of talking about organ specific stem cells. To what extent do we have pluripotential that can move to the area of injury and address the limited space in the brain or the heart.

Doris Taylor: Think about it. If we, if we actually think back to the history of medicine, we have been doing stem cell transplants since the fifties when we did the first bone marrow transplant.

Victoria Maizes: Right.

Doris Taylor: We just didn't realize at the time that the bone marrow had quote stem cells in it because we didn't have a definition for those cells. We thought we were just repopulating white blood cells and the blood system. We didn't realize there were cells in our bone marrow, our blood that actually have the capacity to be trafficked to these sites of injury.

Victoria Maizes: Okay.

Doris Taylor: Mediate repair. So we do have stamp it

Doris Taylor: immature cells in our body that are stem cells that are capable of repairing multiple tissues. However if we're being really clear for the most part, we don't have many fluripotent stem cells that can give rise to all types of tissue, they typically get restricted. We have mesodermal, endodermal. We have cells that are actually tissue system specific. But the cool thing is that our bone, marrow and blood do contain immature cells, that when they go to a specific organ, get the right cues. What does a stem cell do? The whole definition of a stem cell is that it responds to its environment.

Victoria Maizes: Hmm.

Doris Taylor: And becomes like the cells around it. And one of the flaws in stem cell therapy in my worldview has been that we take these healthy cells and we put them in this hostile, inflamed environment. And we say, “Oh, become healthy, normal heart, or become healthy, normal brain or become healthy, normal liver”. And we're it's like we're putting them in an environment with no food, clothing or shelter and staying thrive. You know, and do the right thing. They don't. And, in fact some of the data from the nineties showed that when immature cells, bone marrow derived stem cells were put in the hearts of in preclinical studies. So in animal studies originally, those cells in the middle of the scar turned into cartilage and bone and fat. Yeah. And and people were like, why is that I'm like Duh location, location, location. I wrote a paper called the real estate approach to Stem cell therapy. So part of what I believe is that it's not just about getting the right cells there. It's about also recreating the appropriate environment. 

Andrew Weil: My impression is that we may be close to being able to regenerate severed spinal cords and islet cells in the pancreas, but it seems to me the most urgent priorities are brain and heart, how realistic is that goal

Doris Taylor: So it's absolutely realistic. But I and we can get into this in depth if we want. But I'm going to just everyone who knows me knows. I just call it like, I see it. So I'm just going to call it like I see it. I absolutely think it's physiologically possible and doable. And if you think about a heart attack is when a blood vessel in the heart gets clogged, a stroke is essentially a heart attack in the brain. At least one type of stroke is. Is that realistic? Yes, however, why so? The 1st stem cell therapy was done in the heart in 2000. Why don't we have an approved therapy now? Because it's about choosing the right cell at the right time for the right patient and getting it there and the clinical trials that were done weren't designed to answer those questions. My personal belief is that the system to do clinical trials is somewhat broken. But I want to. And I but I actually want to make another point, can we do it. Yes. Will it take stopping and rethinking the right trials? Absolutely. And it's going to take people who've been in this field for a long time to say, you know it hasn't failed, we just haven't done it right. So let us do it right. Let us own that we didn't do it right. And let's design the right trials now, and actually show that it works.

Victoria Maizes: I want to go back to a place where stem cells has been FDA approved, and very successful, and you brought it up already we have done bone marrow transplants, for example, for people with leukemia since the 1950’s, and while it's a very hard therapy to go through, it's often lifesaving and puts the cancer into remission in that particular situation, it is not the person's own stem cells, it's a donor.

And I just want to understand, based on what you're saying. What can we learn that made that particular use of stem cells effective, part of standard of care for certain kinds of cancers? What's different about that than treating a heart or the brain?

Doris Taylor: First of all, if you think about bone marrow transplant it's as you said, it's a very difficult procedure, and one of the things you have to do is essentially wipe out everything that's already there. Our bones, however, are, all of our long bones, and our sternum are designed to be a reservoir for stem cells. Our body knows how to for bone, marrow and other cells, and our body knows how to grow the cells in that environment, right? So when a stem cell transplant is done, there doesn't always work, doesn't always engraft. But if it engrafts actually, the the few cells that go in start repopulating. And one of the things about stem cells that is unique is, they can regrow a lot more times than other cells that are already more differentiated, so they can just continue to proliferate, and they actually refill the whole bone marrow reservoir throughout your body. But that takes months, and months and months. The only thing you can't change about any of this regenerative medicine or anything is the time frame of biology. I wish we could speed it up. But cells grow how they grow. And you don't want them growing faster. Because that's what happens with cancer cells. So why has that worked, and putting cells in the heart, or brain, or liver, or kidney, or whatever has not.

Victoria: Or knee or hip.

Doris Taylor: And actually, some people would argue, those have worked.
But again, it's getting the right cell in the right place at the right time and we've had 50 years of figuring out that in bone marrow transplant. I guarantee you the 1st X number didn't work like anything that said in an organ like the heart or the brain.

If you the potential to get it wrong is dangerous, right? So you hope that worst case, you do nothing best case, you do something positive. What you can't afford to do is something negative, right? So the trials that have happened in heart and brain are actually more constrained than those that are done in other areas. The number of cells you can give the location of where you can give those cells, how you can get them there. Those are actually very particular in the heart and brain, and and actually have not probably been evaluated to the degree that they need to be. But let me back up and make I want to make. There's one point that I do want to make, and it's not a popular phrase today, but stem cells differ in men and women and they differ in men and women. In part, I believe, because this, the cells in our bone, marrow and blood are the cells that also make up our immune system, right? That inflammation, and the one thing stem cells do better than anything is, turn off inflammation that's their best effect. When you get an injury, you get acute inflammation. That acute inflammation is nature's cue to say, “Help, send me cells”, and if you get the right cells there, you turn off that inflammation, and it goes down and your body repairs itself. If you don't get the right cells there and you don't turn off that inflammation. That's when your body ramps up the inflammatory response and said, “Hey, I said, send me cells”. And then you start getting pro-inflammatory cells there and other deleterious cells that can actually mediate injury rather than repair. Okay, so that's number one.

I want to go back to men and women and and where I said, I think clinical trials are being done wrong. Most of the heart cell clinical trials recruited on average, 17% women, even though women are at least 50% of the population. So they weren't powered to evaluate the effect in women. Okay? And by that I mean, there weren't enough women enrolled to do the statistics properly. Okay, to say this has the same effect in women as it does in men. If we separate that, however, there have been a lot of trials done and the data for women were not reported separately than men, even as supplemental analyses in the papers. Okay, there was what's called statistically an adjustment for someone being a woman. Well, I went back and I said, Okay, if we really believe stem cells are different in men and women. Let's get access to all the data where we know women receive cells and men receive cells. And let's look at the women at the beginning of the trial, the men at the beginning of the trial, and at the end of the trial.

Well, we found 2 things that are really important. One men and women were different at the beginning of the trial women had a higher ability of the heart to squeeze, called dejection fraction the amount of blood that gets squeezed out of the heart.

The one of the endpoints for all of these trials was ejection fraction. So women had higher men had lower. Mix those together. You get so much noise that you're not going to see an effect. Number 2. At the end of the trial. When we went back and looked differently in the the overall trials were negative. In women bone, marrow, mononuclear cells decrease, stroke, decrease, recurrent decrease mortality.

So here's a therapy where the trials are negative, but because we didn't look by sex.

Women are not getting a therapy that could save their lives interesting. More women die of heart disease than men.

Doris Taylor: When we looked at cells in men and women had more reparative cells. Men had more pro-inflammatory cells.
Andrew Weil: why then, do women get more autoimmune diseases than men?

Doris Taylor: I would argue, it's because the balance of the immune system to allow pregnancy doesn't actually fight off foreigners. It fights chime, chimeric things that include self.

Andrew Weil: Where do we get stem cells for this kind of therapy? And is there value in harvesting umbilical cord blood and banking it?

Doris Taylor: I'm a believer in banking, and the reason I'm a believer in banking is because if you need those cells they're good cells, but you have to bank with someone who knows what they're doing, and has demonstrated that they can keep those cells for a long period of time. Because so you have to use a good bank that said and and also there is a there are public cord blood banks.

Cord blood is actually a great substitute for bone marrow. If a bone marrow donor cannot be found and that is often true for people of color or people of different to match backgrounds. Cord blood is, doesn't have to be as well matched as bone marrow. So I'm a strong believer in it. If you need it, you want it. You may not, God willing, you'll never need it. That said, find a reputable bank, or give it to a public bank that's doing this and making it available to everybody. If you're not going to save your own. Where do cells come from? You can get your own cells harvested from bone, marrow, blood, fat muscle almost anything you can get access to. You can get cells harvested from the typical cell therapy that happens if it's your own cells these days…if it's done in a clinical trial, is fat or bone marrow.

Doris Taylor: If it's done at a clinic, it's usually fat. I want to say in the US right now there are over 5,000 unregistered, illegal stem cell clinics and there some are doing good things. Some are not. I'm a strong believer in educating people. So one of the things I've done is create a list of questions that I want to know the answers to before I would get cells or let someone I love get cells. Happy to share that with you all for you to look at. Edit post

Victoria Maizes: Let me ask you a question that comes up a lot. I often get asked by people who have an arthritic knee or hip. They don't want to have a hip replacement or a partial knee replacement, and so they find out that they could have stem cell. And they love that option, because it seems so much less invasive. It's usually not covered by insurance. And is pricey. And what do you tell people like that? Do you say? Absolutely, you know. Just ask these questions. Or do you say, you know, this is still an area of active research. What's your response?

Doris Taylor: My response is, if you go to the FDA website, at least previously, it said, “Don't do it. This is not approved”. What I would say is, if you're going to do it, ask these questions get comfortable with the answers to these questions. Go to reputable sources, not people who are just sharing testimonials, people who are willing to share data with you. And then there are some therapies where the devices to make the cells have been vetted and approved by the FDA. Those kinds of situations where either the laboratory has been approved by the FDA or the device that's actually isolating the cells has been approved by the FDA. That increases my confidence. But your average provider, I'll use that term on the street… I encourage you to ask questions, ask questions, ask questions that said, does it work?

The reality is they are beneficial. They do change the inflammatory cascade and part of what I think we need to do in this country is create a registry. Enabled these people who were doing all these treatments to actually supply data require that people do follow up. 

One of the catches is people come into a clinic, you go in, you get your knee treated, you go away. No one ever knows if it worked or didn't work. And if it did, and you happen to be the one person who it did. You then become the spokesperson for that clinic? Right? So we need data.

Victoria Maizes: So in the US that's usually an autologous stem cell transplant meaning it's probably coming from bone marrow, or fat,

Doris Taylor: Actually, what happens for joint most often Is you go in. Somebody draws your blood they either make platelet-rich plasma or they isolate some of the white blood cells along with the platelets and plasma, and get rid of some of the cells, and then put that back in your body. And the things I say to people is okay, if you're taking my blood and you're going in the other room, I want to know what you're doing in that other room. I want to know it's sterile. I want to know how many times have you done this? Have you done this in 100 people, or have you done this in 100,000 people and do you follow up? And can I see the documentation? Ask the questions. And then you know, who am I to judge that for other people, except that if it were me or my family, what I say is let's get let's get informed, you know elite athletes have been doing this for 30 years. People have been going out of the country to get it done for decades. Now some of those places have good records, some don't. And the only way you're going to know is, ask I don't know if people have seen this, but there's a podcast called the Bad Batch and I was in Texas when that whole fiasco happened, because Texas became a right to try state where, if you had a chronic illness, and a doctor would prescribe it. You could go to anybody and get stem cells and a chiropractor delivered stem cells to a number of people. However, those cells were contaminated with bacteria, and the majority of those people who were seeking therapy for serious diseases ended up in the ICU, very, very sick from a bad batch

Andrew Weil: Given the effect of stem cells on inflammation is that, do you see a role for stem cell therapy in autoimmune conditions?

Doris Taylor: Absolutely, and cell therapy is actually beginning to be approved for autoimmune conditions. Absolutely. I do. I mentioned cells are different in men and women.

Doris Taylor: What we've shown is that the incidence of heart disease in men and women actually parallels the loss of certain stem cells. And it's it's actually just you can draw the inverse curve. We've done that. The data are pretty beautiful. And we also showed that in women with heart disease, they have a different TH1 TH2 balance than men, so they develop a different kind of heart disease. And women who have the same inflammatory profile as men actually develop the same heart disease as men. So it's absolutely related. I think we'll see approval for cells for the use in autoimmune diseases, graft versus host disease. One of the first conditions where somebody who gets a bone marrow transplant and that bone marrow, actually their body, it reacts with their body and causes a massive, immune response…there are certain cells that will mitigate that whole body inflammatory response. So yes, absolutely. 

Victoria Maizes: So autoimmune disease. Would that be similar, then, to someone who has a cancer where you really don't want to use their own cells

Doris Taylor: So let me back up and say so cells are being used. If you think about it, CAR-T therapies have been developed in the last couple of years. And CAR-T therapies are basically a cell therapy for people with cancer and the approval of this T cell therapy, where the receptor on the surface of the T cell has been modified using some genes actually, then growing those cells to fight the cancer has been the biggest breakthrough in the potential for approving stem cell therapy. And those are self-derived. Typically, okay, so CAR-T therapies, even though the cells are modified, they come from the patient.

Doris Taylor: Think most of the people out there who are getting non-umbilical cord blood cells are getting their own fat-derived cells. There's a difference, though, in getting fat, derived cells that are grown and stored, and the cells that come from your fat and are given back to you within a few hours. And there's a very big difference in the potency of those cells. I have my own beliefs about which one is best.

Doris Taylor: Yeah.

Victoria Maizes: So give us a summation. We are in this world of FDA approval. In one area, rapid development in some other areas like autoimmunity question marks in the heart and the brain, because there's still so much that we don't know in terms of the timing and the number of cells give us give us a summation. Where are we in the US. At this point, and where might we be in 10 years?

Doris Taylor: So cell and gene therapy, regenerative medicine is happening. The question is not if it's when it will all be approved.

Doris Taylor: And I think in summary, I would say the unmet need is, great.

Doris Taylor: People don't have good alternatives, and so they're seeking these regenerative therapies. And that's why there are 5,500 stem cell clinics in the Us. Right now. But the thing to remember about cell and gene therapy and other regenerative medicine strategies, unlike anything else like a drug is. Once you get it, it doesn't just go away in 24 hours, and we can't take it back. So it has to be as pristine as possible. So in summary, I would say the path for approval is clinical trials. Clinical trials are happening very slowly. They're expensive. We haven't redesigned them. We're not letting people have access to a therapy. If the trial is positive. There are a lot of things that need to change there. And until they do people are going to seek these therapies elsewhere. 

Andrew Weil: So we would love to have your list of questions if you would share that with share that with patients

Victoria Maizes: Yeah, thank you so much for coming on.

Doris Taylor: Thank you.

Victoria Maizes: Body of wonder for sharing your knowledge in this rapidly evolving area of medicine that obviously has tremendous potential and also potential risk

Victoria Maizes: Yeah, thank you. Thank you so much for sharing

Doris Taylor: Thank you. It was a great conversation. Thank you both

Andrew Weil: Bye-bye.

Doris Taylor: Bye.