领先的干细胞专家：干细胞101——医学的未来，与 Robert Hariri 对话｜第147期

Hey buddy, good to see you. I have a question for you off the bat: I can go to Panama, Costa Rica, Mexico, or Antigua. I can even go to Bali, where Genting just created a stem-cell facility, and get stem cells as an American citizen, but I can’t get them in the United States. When are they going to be legal here? When are they going to become available?

That is a great question—one that has been plaguing all of us in the industry for decades now. It’s really a phenomenon related to the very conservative regulatory nature of the FDA and the systems at work behind testing, validating, and proving the safety and efficacy of therapeutics.

I personally believe that we’ve been working with stem cells in one form or another for over 30 years. In fact, bone-marrow transplantation is stem-cell transplantation, so this has been around a long time.

My personal perspective is that cell therapy, in almost any iteration, in its unengineered form, is intrinsically safe. That’s why a lot of jurisdictions—particularly in Asia, and increasingly in Eastern Europe and the Middle East—are very receptive to providing an abbreviated pathway to approval.

When you ask whether they’re legal, what you’re really asking is whether they’ve been approved by the regulatory community. I think the United States is behind the times on this. What it needs is a little bit of courage and a willingness to accept the fact that the therapeutic potential of these things outweighs the nominal risk of some uncertainty about long-term safety.

We’ve been doing stem-cell treatments in patients for decades and decades, and we do not have a long-term safety signal that should concern people. But I do believe there are other forces behind this very resistant approach to approving and making these products available to patients.

We know so many people who have had significant positive impacts from cellular medicine and stem cells. I think of it as one of the fundamentals of the pro-longevity and regenerative-medicine decade ahead of us, and it’s sad to have to flee the country to have access to this technology.

I’m biased. I’m your vice chairman at Celularity, and Celularity is a cellular-medicine company. Full disclosure: Bob is, in my mind, the leading figure in this field. He’s the first person to give me what I would call massive enthusiasm—or even religion—on stem cells.

I want to do a stem-cell 101 for people to understand what stem cells are, why they’re valuable, and why people are flying to the clinics you and I have written about. In the book behind you, Tony Robbins’s photo is on the cover, and the opening chapter talks about him having this massive accident and going down to Central America for stem-cell therapies instead of going down the street to do this.

Everybody understands that, at the moment of conception, when sperm and egg come together, a single cell is created. That is the first primordial, what we call totipotent, stem cell. From that single cell, every cell that ever occupies your organs and tissues is derived—all 40 trillion cells that make you up, and all 40 trillion cells that are renewed and recycled over and over again throughout your life.

Think about the replication fidelity of taking one cell and making perhaps 20,000 to 300 trillion cells in your lifetime from that single cell. That’s where the power of stem cells really resides.

Let me take a step back and explain, in a broader way, the significance of this biological process. We all come from a single cell—the first stem cell that exists with our DNA composition. Those cells divide, and some of them specialize to become brain cells, hair cells, bone cells, and heart cells. That specialization process is called differentiation.

What’s really cool about stem cells is that they reserve the right to specialize or make a copy of themselves. That’s what keeps our system capable of going through this constant renovation and renewal process.

It’s important to keep in mind that the stem cells in every tissue of your body are your natural repair kit. After conception, from that original totipotent stem cell, numerous other versions of these cells emerge. Some take on the characteristics of a certain tissue type—that’s called a tissue lineage—and go on to build the final tissue and organ. They build the heart or the brain, while others remain in stem-cell form.

Those cells sit there in what you and I often call the regenerative engine. That regenerative engine resides in every tissue and participates in the renovation process that keeps us healthy and young.

Let me slow this down for a second. You’re saying that we start with one cell, which replicates and eventually forms a full embryo. My niece is delivering today, and she has a LifebankUSA kit there to store her placental stem cells. We’ll get to that in a little bit.

That original totipotent stem cell—as opposed to a pluripotent stem cell, which we’ll define in a minute—becomes every tissue type. It becomes skin, bone, ligament, cartilage, neurons, heart, lung, and everything else.

Those are the cells that differentiate into a tissue type, correct? Within every tissue in our body are stem cells that can then differentiate into the appropriate tissue. In the lung, they can become lung tissue; in the liver, liver tissue; and in the brain, brain tissue.

You used an amazing analogy that I love, and I’ve used it often. I just wrote about it in my Longevity Guidebook: the repairman in the mansion. Would you give that analogy again?

Just as you renovate your home to keep it in perfect operating condition, it’s best to renovate with the original materials that were used to build it in the first place. That’s one of the reasons good contractors will often leave you a supply of tiles, countertops, plumbing supplies, and so on. As you go through the process of repairing things over the years, you’re repairing them back to perfect condition.

Nature does that for you by keeping a small supply of stem cells in every organ and tissue of your body. Those stem cells are called upon to perform the repair process. They’re your natural repair kit.

Over time, you exhaust that supply. We often think of the aging process as involving one of the hallmarks of aging: you simply use up your stem-cell reservoir. It makes sense. Just as you use up the extra tiles left over for renovating your bathroom, you can use up your stem cells as well.

It’s important to keep in mind that what makes a stem cell valuable and useful is its ability to specialize in a versatile way. It doesn’t necessarily have to be fate-directed. Stem cells in your liver have the ability to become hepatocytes, the actual liver-metabolizing cells, but they can also become biliary-tract cells, blood-vessel cells, or support cells. They choose their fate based on demand.

A lot of that fate choice is directed by where the cell is. Every tissue in our body is a combination of a structure and a template occupied by cells. That template provides chemical signals that tell the cell where it is.

I often say it’s like walking into a mall, looking at the map, and seeing the words, “You are here.” Now you know how to find Abercrombie & Fitch or whatever store you’re looking for. The same thing happens in the body. The different cells and stem cells in a tissue know where they are and specialize in an appropriate way.

If I inject stem cells into your bloodstream and they get to your liver, but they don’t yet become liver cells, they don’t eventually make a mistake and become a brain cell. That specialized maturation process is very much orchestrated by the environment.

One thing that’s important to discuss is what happens as you age to your stem cells. I would call it stem-cell exhaustion, and this is research that you’ve done and brought to the industry.

How many stem cells do you begin with as a newborn, and where do you end up at the end of life? It’s another version of your mansion story. Imagine you built a giant mansion. In the beginning, your mansion has a whole bunch of repairmen and perfect instructions. As the repairmen keep things going and follow the instructions, the mansion stays in great shape.

Eventually, the repairmen and women start to die off, and the population of people able to repair the mansion begins to degrade and eventually fall away. The instruction set begins to blur and deteriorate. Your ability to keep the mansion in good structural health disappears. You’re getting the same thing with stem cells, so talk to us about the changing populations.

Every stem cell retains what I always call the fully transcribable genome. Our biological software is in our DNA, in our genetic material, and that software is used to make all the necessary chemicals, proteins, and signaling molecules that drive the functionality of every cell in our body.

Those functions differ based on the organ or tissue. Liver cells have part of their genome dedicated to liver functions, and in the process of becoming a liver cell, part of the genetic material gets silenced so the cell can be very efficient at what it does.

The stem cell, in contrast, retains all that versatility—the ability to read the whole genome. When we first began building our interest in this field, we created a company called Human Longevity. Human Longevity was dedicated to interrogating the genomes of long-lived people to better understand what might be a hallmark of long life.

Our former partner, Craig Venter—the first scientist to sequence the human genome—always spoke about DNA as biological software. I spoke of stem cells as the minicomputer. The software resided in the nucleus, all the reading and writing of that software took place in the cytoplasm, and the surface of the cell acted like a keyboard.

If you think of it in that model, what makes a stem cell so valuable is that it’s like a perfect, uncorrupted reboot disk—a master boot disk. As long as you keep it in good condition, anytime your software gets damaged by mutation, exhaustion, or chemical adulteration, you can reinstall the software with this master boot disk and get back to a state of high health and high functionality.

Anyone under 35 may not know what a boot disk is, but it was what you used to get with your computer to boot it up and initialize the disk drive. The analogy still holds.

One of the things you mentioned to me is that, between birth and death, you get something like a 100- to 1,000-fold reduction in the number of stem cells in each of the tissues of your body. Is that true?

We know that a hallmark of youth is an abundant, healthy supply of stem cells. Let’s look at one organ system: bone marrow. People know that bone marrow makes the blood—the red blood cells, white blood cells, and platelets. Bone marrow is filled with stem cells that do all that work.

Early in life, after birth, if you measure the number of stem cells in the bone marrow of an 8-week-old, about 1 in 20,000 to 30,000 cells in the bone marrow of a newborn is a stem cell. Over your lifetime, that number declines exponentially. If you look at the bone marrow of an 80-year-old, it’s 1 in 20 to 30 million.

That’s a 1,000-fold reduction.

Exactly. It should be obvious to everybody that the more stem cells you have, the more you’re able to respond to the need for repair and regeneration. As you get older, if it’s harder to find a stem cell to do that work, you’re not going to repair back to the same state of function and health.

Think about it as using up your toolkit supplies.

You’ve talked about stem cells as the regenerative engine of your body. People who have heard these conversations about longevity know that we’re typically in peak condition in our late 20s—around 27 to 30 years old. Then there’s a slow decline: loss of muscle, loss of immune function, loss of hormonal balance, and, very significantly, loss of stem-cell capacity.

You can accept that and accept your fate, or you can fight against it. One of the things you’ve been leading the charge on—and I remember the first conversation we had about it, when I thought, “This is incredibly exciting”—is the idea of stem-cell supplementation.

There’s the idea of storing your own stem cells, which we’ll get to, and also using placental stem cells to augment your stem-cell populations and even your immune system. I want to talk about using those to augment your stem-cell populations rather than accepting what is and saying, “No, I want to restore my level of regenerative capability in my body.”

That is the vision, and I feel confident, based on the work that you and others have done, that it is definitively possible. Before we get to how you got into this field, let’s talk about the different types and origins of stem cells. There are many different types. Let’s define them, their utility, and where people might have gotten them when they say they’ve received stem cells.

You touched on two important concepts. First, if we could augment or supplement our reserve of stem cells with a supply of stem cells that’s available, that would be a good thing. We already know it’s well accepted in the scientific community that a hallmark of aging is exhausting your stem-cell supply.

It’s intuitively logical. If my body repairs itself with stem cells, and I run out of stem cells, I stop repairing myself. The first concept is that supplementing or augmenting your stem cells is a good thing.

Thirty years ago, I said, “Since I know I can get stem cells from the leftovers of a healthy pregnancy, and it’s easy for me to isolate those cells and put them into a state of suspended animation by cryopreserving them—freezing them at ultralow temperatures—if I need them later in life, can I thaw them out and use them?”

The concept is true. You can do that, and that’s the whole foundation of the newborn stem-cell banking industry, which has been around for more than 30 years.

The second concept is that you can use those cells later in life.

Before we go there, you mentioned the leftovers of pregnancy. Just to give people an image: when an embryo is in utero, it’s getting a supply of cells from the placenta. I use the term—and thank you for crediting me with it—that the placenta is a 3D printer that manufactures the baby.

The placenta has the stem cells—the original boot disk, as you call it. Normally, in the labor-and-delivery room, you pay a fee to have your expelled placenta burned in an incinerator.

It’s crazy, because it’s like throwing away an extra set of organs for your child.

That offended me. It offended me to see this beautiful tissue being discarded. People would say, “Bob, why is a neurosurgeon chasing placentas?” They thought I had lost my mind.

The reality is that I recognized this as pristine tissue. It’s the age of the newborn, and it has structure, function, and cellular content that are about as good as they’re ever going to get.

Most importantly, as you said, it’s simply paid to be disposed of. All you need to do is come up with an industrialized process to utilize those materials and cells.

The placenta is an ideal place to get leftover cells. It all started when we recognized that you could find blood-forming stem cells left over in the circulating blood of the umbilical cord at the time of birth. You clamp the cord, cut the cord, the baby and a little piece of cord go one way, and the placenta and the umbilical cord go into the wastebasket.

My concept at the beginning was, why let it go into the biohazard wastebasket? Collect it, process it, and use what we know about cryopreserving cells to store them away forever.

I want to break that down for a second. One of the divisions that Celularity has is LifebankUSA. A lot of people have heard of cord-blood banking, where you take the cord blood, which has hematopoietic stem cells—blood stem cells.

That has always been the biggest industry, but it’s missing the point. What you really want are the stem cells that make up all of the tissues of the body, and those are in the placenta.

LifebankUSA is where someone listening who’s having a baby can go. My 2 13-year-old boys were born 13 years ago, and we stored the cells from their placentas. You have a room full of cryogenic freezers, and I’m always saying, “Bob, where are my kids stored?” I go over and say hello to their stem cells.

Now, 13 years later, my niece Christina is having her baby today, and they have a LifebankUSA collection kit. They’ll collect the placenta and some cord blood, and it gets shipped to you for processing. Her newborn will then have those cells stored.

I think it’s a moral obligation for any parent to save that for their child.

I couldn’t agree with you more. Thirty-some-odd years ago, I give my older daughter Alex credit for this. When I was a young surgeon and she was in utero, I went down to see the first-trimester ultrasound. I tell you the story all the time: I looked at her little peanut-sized embryo, but the placenta was already a big organ.

I said to myself, “In medical school, we were taught that the placenta was a vascular connection between the mother and the developing baby.” As an engineer, when I looked at it, that didn’t make sense. If she was only the size of a peanut and the placenta was already a big organ, it suggested to me that the placenta played a role in making that embryo become a fetus and beyond. It was participating like a 3D printer in printing the baby.

You said something very important: if you look at an embryo, there simply aren’t enough cells in an embryo—even at the maximum rate of division—to build a baby in 9 months. Some of the additional cells necessary to build that baby have to come from somewhere. They come from the supply depot, and the supply depot is the placenta.

The placenta is a valuable asset to a family. We’re talking to government leaders in certain jurisdictions, because this should almost be a medical imperative. If you have this supply of repair and starting material, you may be able to prevent and interrupt disease progression.

We’re in the era of cellular engineering. You can fix things. If I have your placental stem cells stored, that’s the perfect blank canvas to subject to all these new ways of editing the genome, creating immune cells that target your disease, or fixing immune cells that give you autoimmunity.

All these things are possible if you have the raw-material supply. Almost 20 years ago, I did a little Skunk Works experiment in which I collected stem cells from the placenta of newborn rats, processed and stored them, and gave those rats their stem cells back as they aged. The animals lived 40% longer than the untreated animals.

I want people to recognize that you can get stem cells from the placenta. Some companies will give you stem cells from the umbilical cord, or cord blood, but there are a few other options for where people get stem cells. Can you run through those?

In an effort to make stem cells available to people, technologies like induced pluripotency were created. Shinya Yamanaka won the Nobel Prize for figuring out how to take one of your mature, specialized cells and reprogram it so that it acts like a stem cell.

That was important because not everybody had their placenta or cells stored at birth. But I’m here to tell you that, as phenomenal and exciting as that technology is, it’s going through a lot of acrobatics to make an adult cell behave like a placental cell.

Even though you might turn on pluripotency, you don’t change the age of that cell. There are other parts of the cell besides the parts that get reprogrammed that age. Mitochondria age, cell membranes age, and so on.

I’m here to say that the placenta is the ideal alternative, even if you don’t have your own cells banked. That was one of our seminal breakthroughs and discoveries early on: aside from the fact that the placenta is the stem-cell factory, the cells in the placenta are nature’s universal donor cells.

You’ve talked about this concept before.

Mom and Dad contribute 50% each of the DNA of their offspring. The fetus and its placenta growing inside the mother’s womb are only a 50/50 match to the mother, yet she doesn’t reject it, and it doesn’t reject her.

What about a surrogate pregnancy? In a surrogate pregnancy, the mother isn’t even related to the placenta or the fetus being developed, and she doesn’t reject it.

It’s proven by nature. Mammalian evolution could not have occurred without the placenta becoming a perfect universal donor tissue, able to tolerate the existence of a different genotype. That’s the elegance of the placenta: I can use those cells in a completely unrelated recipient.

There are autologous and allogeneic cells. Can you explain those concepts?

“Auto” means the cells come from you—from the self. You can get stem cells from your blood, bone marrow, or adipose tissue. There are lots of places to get your own stem cells.

You can also take a mature cell, such as a fibroblast from your skin, subject it to Yamanaka’s methodology, induce pluripotency, and create a stem cell with the versatile ability to divide.

You can get stem cells from pericytes, the cells associated with blood vessels. You can get them from bone marrow, from peripheral blood into which you mobilize stem cells from the bone marrow, and from virtually any tissue if you’re willing to take a scalpel to that tissue.

In contrast, there’s no risk in collecting cells from the placenta. It’s waste material. The baby is already born and off enjoying its life. When the placenta is expelled, it goes into the wastebasket, comes to our laboratories, and gets processed. From one placenta, we can produce tremendous quantities of stem cells.

“Allogeneic” refers to cells that come from somebody else. In those cases, if they aren’t derived from an allogeneic placenta, you have to make certain there’s no immunologic conflict between the donor and recipient.

Allogeneic therapy is really the hallmark of efforts to create off-the-shelf cell-therapy products. Autologous cell-therapy products—for example, immunotherapy for cancer—mean that you have to collect your own cells, process them, and get them back at some point in the future.

There’s been a lot of controversy over the years about stem cells, and a lot of fear and concern. Where did that originate? What have people heard that caused this concern, and how can you assuage their fears?

From medical-school embryology, we know how we originate from a single cell, become an embryo, and then form a fully functioning human being.

That original work led scientists to look at leftover embryos from in vitro fertilization programs—embryos that were going to be discarded because they weren’t used—to see if they could isolate some cells and grow them into a population that could potentially be used in therapy.

That meant destroying an embryo. The controversy that erupted was based on the fact that, at the stage when you can isolate stem cells, that embryo still has the potential to become a human being. Does it constitute a life that you should not be allowed to compromise or sacrifice?

That was the fundamental origin of the controversy. You could also get stem cells from stages further along in development, from a fetus, as a byproduct of abortion. Scientists showed that they could isolate stem cells from the leftovers of the abortion process.

This put a significant part of the community under great concern that there could be a very perverted incentive to create human life in the form of an embryo or fetus just to destroy it. The pro-life and pro-choice debate was the foundation upon which the controversy around stem cells emerged.

I’m very happy to say that our discovery of the placenta as an ideal alternative addresses that. The placenta is pro-life and pro-choice. There is no objection to using the leftovers of a full-term, healthy pregnancy to derive stem cells.

It’s abundantly available, the economics are better, and if I can get a dozen cells from an embryo, I’m lucky. I can get a billion cells—easily, multibillion cells—from a placenta.

The sheer logistical convenience of using the placenta, combined with all the characteristics I’ve described—the immune-tolerating ability and universal-donor characteristics—makes the placenta an ideal source. It obviates the need to use embryos or fetal material.

I want people to understand that the original controversy and concerns came from the idea of using embryonic stem cells from an abortion or a fetus.

Today, the stem-cell industry has matured far past that. We can give you back your own stem cells. We can extract them, concentrate them, and manipulate them in a number of ways. We should talk about that again, because it’s not yet FDA-approved—hopefully, under a new administration, it will be.

Or we can give you placental or umbilical-cord stem cells from somebody else. These allogeneic cells are safe and have been used in many treatments. How many total allogeneic stem-cell treatments do you think have been performed around the world?

Millions.

Millions. This isn’t a wild frontier of ideas that someone came up with in their garage and is trying on you.

Exactly. Bad news travels fast. If cell therapy caused bad things—if using stem cells to treat different diseases caused bad things—that news would travel fast.

There have been a few isolated situations in which people with irreversible, hopeless diseases sought cell therapy from, let’s admit it, unscrupulous and opportunistic providers as a therapy of last resort. They were trying everything.

I have a lot of respect for the FDA. The current head of the FDA division that oversees cell therapy, Dr. Peter Marks, has an incredibly complicated and difficult job. He has done an amazing job focusing attention on this field.

He wants to see these therapies approved, but he wants to make sure they’re approved the right way. He wants to make sure there’s never a shortcut in producing the products. I salute and celebrate that completely.

It’s important for people to know that there are a lot of mom-and-pop shops around the country that promise stem-cell treatments. You need to understand their origins and experience, because they’re not legally doing it. They’re operating in the gray zone between a fully developed, regulated therapeutic that meets the high standards of safety and efficacy prescribed by the FDA.

They try to go around that. Groups like ours do the hard work of taking these candidate therapies through the process of clinical development and clinical trials, where we control the treatments, the analysis, and the manufacturing. That’s the best way to ensure that no one takes a shortcut in transforming the way a disease is treated.

But I’ll tell you this much: I do believe there is room to be more receptive and open to accelerating the process of review for cell therapies. This is a little pet peeve of mine: we should take advantage of the long safety track record of cell therapy and allow some of the evaluation to take place on the run.

In other words, there should be some form of provisional-approval process. Cell therapies that meet a high standard for safety should be allowed to be tried, particularly in some of these hopeless diseases.

Let’s talk about ALS, Lou Gehrig’s disease. Nothing works there. If you have ALS, you’re going to die. I don’t see a downside to using a number of cell-therapy products that meet that safety standard and rigorously collecting the data.

It would do us a big favor to open up the number of programs where we’re rigorous about collecting data, so we can make better decisions about what is acceptable or unacceptable to move into the therapeutic armamentarium of doctors.

Let’s talk about the social proof. There have been a number of success stories. I mentioned the opening of Life Force, where Tony called me and said, “I’ve just had the worst snowboarding accident. I’ve massively injured my shoulder. What should I do?”

I told him, “You need to talk to Bob Hariri. He’s the world’s expert in stem cells, and I think these types of injuries could benefit.” He called you, and at that time, we recommended using the Panama Stem Cell Institute. Since then, we’ve seen the emergence of the Regenerative Medicine Institute in Costa Rica under Vince Giampapa.

Most of the people we recommend who need this level of allogeneic stem cells go down there until we have them operational here in the United States, perhaps at Fountain Life. Take the story from there, and tell us about some other success stories you can share.

Tony is an example. You and I fall into the same category: we’re at an age where we break things and tear things. Our bodies make a great attempt to mobilize our own stem-cell populations and get them to the injury to participate in the repair, but sometimes it’s too little, too late.

In Tony’s case—and let’s face it, he’s like a professional athlete times 10. Aside from being 6'8" and weighing 260 or 270 pounds, he’s a physical specimen, and he taxes his body to the absolute limits.

When he tore up his shoulders, tore up his hips, and hurt his back, he either had to go for prosthetic-replacement surgery or attempt to turn up the regenerative power of his body. The only way to do that, because his own cells were too limited, too few, or too late, was to augment them with newborn cells.

As covered in the book, he had a life-changing response. I, too, have had more than 30 orthopedic procedures in my life. My shoulders have been torn up, and I have no rotator cuffs. The only thing that keeps me active is that I have range of motion, and I’ve used cell therapy and the byproducts of cells to stimulate the repair process and tamp down the inflammation that causes functional decline.

I’ll give a quick side note. I ran an experiment—not on purpose, but in retrospect—where I had the same surgeon perform the exact same surgery on my two shoulders about 10 years apart.

It was a bone spur and rotator-cuff injury. I was in pain, couldn’t sleep, and couldn’t move my shoulder. On my left side, I had no regenerative-medicine intervention. On my right side, after the surgery, I had 2 injections of exosomes.

I was 10 years older, and my recovery time was a fraction of what it had been before. The pain was a fraction of what it had been in my other shoulder. It was subjective, but I thought, “Wow, that was different.”

I had the same experience. When I tore up my shoulder, I couldn’t sleep, the pain was unbearable, I couldn’t move it, and I couldn’t load my biceps.

When I had placental cells injected into one shoulder, within a matter of days I had a considerable reduction in pain and an improvement in function. When I tore up the other one, I used exosomes, just as you did, and got very noticeable, quantifiable relief.

Most importantly, it turned off the processes that would lead to long-term dysfunction—scarring, changes to bone and cartilage, and all of that.

We’re proof in practice that this stuff actually works. People wouldn’t be seeking these therapies if there weren’t enough evidence from other people, as well as growing evidence in individuals themselves, that this is an alternative to other forms of therapy.

Can you explain what an exosome is? People have heard about them being used for skin, hair, and all kinds of things. And why haven’t the clinical trials been done that allow the FDA to say, “Yes, this is safe and efficacious”?

First of all, there have been a lot of clinical trials. I don’t necessarily agree with how all the data has been analyzed and interpreted.

I believe the bar for proving efficacy in cell therapies has been unusually high. The best examples are in the treatment of heart failure after myocardial infarction. Once you damage your heart, it’s damaged. You can’t fix it unless there’s a regenerative event taking place.

I think the bar has been very high because we’re using 20th-century methodology to evaluate clinical trials involving 21st-century technology. The metrics have to be reevaluated, and I think the time course for looking for changes has to be lengthened.

The rate limiter for clinical trials is time and cost. If you need a lens that looks at the results of cell therapy 6 months, 1 year, or 2 years down the road—and across multiple treatments—it becomes cost-prohibitive for companies in this field to do those studies.

There are no big companies doing stem-cell clinical-development work. They’re all developmental-stage biotechs, and developmental-stage biotechs can do only as much as the capital they raise allows them to do.

The odds are against getting to the point where you meet those very high regulatory standards. But I believe that, in partnership with regulators, we have to say that products with no doubt about their quality, made under the quality systems of good manufacturing practice, and subjected to the right release-specification testing and evidence of acute and long-term safety should be allowed to enter treatment regimens.

There’s also a very high likelihood that cell therapy in combination with other elements of conventional therapy is where you get the real return on investment—the real benefits patients need. We’re not doing that because the regulatory system isn’t designed to look at things that way.

I think we’re at a stage where regulators can be more permissive. They can allow real-world evaluation of the long-term benefits of cell therapy in products that meet a high-quality standard and have the fundamental assurance of acute safety necessary to get into the clinic.

If we did that, we could build the database. We live in the world of AI and machine learning. What do AI and machine learning need? Big data sets—not 10 patients or 100 patients, but 10,000 patients.

Is Bobby Kennedy’s position pro-stem cell and pro-regenerative medicine?

I know there’s a great deal of concern because Bobby Kennedy is a very outspoken proponent of looking at therapeutics differently from the conventional views out there. But he is very much a proponent of the United States advancing and innovating in therapeutics, among which cell therapy is one category.

I do believe he will find a way to work with partners at the FDA, NIH, and elsewhere who will be far more inclusive and receptive to development models with a longer lens on patient results. They’ll look at a range of outcome variables and test these therapeutics in the context of finding ways for them to fit into conventional treatment regimens, including drugs and other components.

Exosomes—give us a 101 on exosomes. People have heard about them being used for the skin, the hair, and all kinds of things.

Think of an exosome as a packet of materials that includes signaling molecules, growth factors, microRNAs, and all the ways cells communicate chemically. These get packaged in what’s called an extracellular vesicle.

It’s a membrane-wrapped delivery package containing important molecules that can be anti-inflammatory, pro-regenerative, and even help stimulate the expression of certain genes in an individual’s genome.

They’re released by cells, and they can be processed and collected in a manufacturing system. When administered to an individual, because they’re membrane-bound, they fuse with the membrane of the person’s cells and deliver that information into the cell.

It’s like a special-delivery package containing an anti-inflammatory growth factor or a pro-regenerative peptide.

What are some of the other stories you’ve been involved in or seen in the stem-cell success story? I want people to have some sense of how broad this is.

People would be surprised to know that many celebrated theater and movie celebrities who are aging but still facing the demands of a very active physical life have sought cell therapy in one form or another.

Some go to clinics in Europe—Leie [?], for example. It’s not human cell therapy; it’s cell therapy derived from other species. But they know that the benefits for anti-aging, performance preservation, and aesthetic benefits are there.

I’ve taken a number of well-known people to different clinical environments in Central or South America, Mexico, and the Bahamas. These people have seen very tangible improvements in a particular need.

The most common reason people seek these therapies is joint problems—arthritis.

Let’s talk about that, because you pointed out to me that muscle mass and longevity are highly correlated. I worked diligently on putting on 10 pounds of muscle mass last year, really through your inspiration and encouragement.

People don’t recognize how important skeletal muscle is. It’s a forgotten organ. People don’t think of it as an organ, but muscle makes up 50% of the wet body mass of the average individual. That means it’s the largest synthetic organ in the body.

The cells in your muscle make up a whole array of chemicals called myokines. Those chemicals influence every cell and tissue in your body, including your brain. That’s why exercise and getting those muscles working are good for your brain health, immune health, and much more.

In addition, muscle is the largest venous-capacitance organ. It has the largest network of small, low-flow, low-pressure blood vessels, and that’s where many of our stem and immune cells take up residence. They’re sequestered there, waiting to be called upon to traffic and do their job.

About 20 years ago, I said that muscle was the forgotten frontier for the therapeutics and pharmaceutical industry. I became very active in finding ways to modulate myostatin, a protein designed to control how much lean muscle mass you make.

I saw that as an opportunity to enhance muscle quality and growth by blocking this negative peptide. We were able to do that with nutritional products, and there are also a number of pharmaceutical approaches.

This is incredibly important because of the study you quoted from the Karolinska Institute, which is the Mayo Clinic of Europe. They followed 9,000 men for 25 years.

What they found was that men who maintained healthy lean muscle mass and strength—even if their body-mass index was considered obese—had a higher resistance to dying from cancer or heart disease than those with any other indicator.

So muscle mass is a better predictor of longevity and health than body-mass index, weight, or any of those metabolic markers.

I keep saying that any company that increases muscle mass is a company I want to look at investing in.

You and I are co-founders, along with Tony Robbins, Bob, and Bill Kapp, of Fountain Life. Fountain Life has done an amazing job on the diagnostic side. We upload about 200 gigabytes of data through full-body and brain MRI, a DEXA scan, coronary CT with an AI overlay, low-dose lung CT, blood biomarkers, full genomics, metabolomics, microbiome data, and a lot more.

The goal is to answer 2 questions: Is there anything going on inside you right now that you need to know about? And what’s likely to happen to you that we can prevent by optimizing you?

That’s half of the objective. The other half is finding disease at the earliest stage, when it’s most treatable. You and I have always had the vision that the diagnostics are important, but the therapeutics are just as important.

How do we deliver the highest-reward, lowest-risk therapeutics to our members? We search the world for those therapies and deliver them at our centers. I want to get your thoughts, because I think we’re just at the brink of a lot of exciting longevity therapeutics.

The goal is to restore function. You’ve taught me to think about whether you’re thinking clearly, looking good, and moving well. That’s what people want through their 99th birthday. Are we going to be able to deliver therapeutic stem cells, exosomes, and other things through Fountain Life? What’s your vision?

You and I have talked for a long time about what’s meaningful. The concept of anti-aging and longevity has been somewhat perverted over the years. It can seem like the folly of the wealthy, and there haven’t necessarily been morally justifiable reasons for wanting to live to 150.

When I was a kid, there was a television show called The Immortal. I loved that show. The main character had blood that allowed him to live forever, so he was hunted by billionaires who wanted to take his blood.

Here’s the bottom line: meaningful long life requires preservation of performance. I always say it’s about high-performance mobility, as you said; high-performance cognition; high-performance immunity; and youthful aesthetics.

Those 4 things, in my mind, constitute meaningful long life. They’re all achievable through many different approaches—nutrition, exercise, maintaining muscle mass—but they’re also the perfect targets for the regenerative therapies available through cellular medicine.

When we first built Human Longevity and then decided to perfect it in Fountain Life, our objective was to do 2 things. We wanted to use a proactive approach in health care to identify and eradicate the causes of premature death.

Life expectancy is an average lifespan of everybody. If it’s 78 or 80 years of age, and we know people live to 95 or 100, a lot of people are dying early.

Step 1 is to eradicate the causes of premature death. What are the causes that get away from us? They’re cardiovascular disease and cancer.

The cardiovascular causes include explosive events such as aneurysm ruptures and cardiovascular failure due to electrical issues that cause sudden cardiac death. There are also undiagnosed cancers that are so advanced by the time you find them that they can’t be managed.

Anything that can identify those problems early enough to intervene is a principal target of Fountain Life. We’ve already proven that it works. We’ve saved hundreds of lives—hundreds and hundreds of lives.

We’re saving lives in the first community that has access to this technology: informed, educated, affluent people who are already receiving the best health care.

How many people do you and I both know who have religiously pursued health care with the best physicians and received a clean bill of health, only to come into Fountain Life and have us identify something?

Sam Nazarian, who has made this public, is one of our new partners building out centers around the world. I was taking him to meet Richard Branson on Necker Island, and we stopped at a Fountain Life facility.

He and his wife went through a workup. This is a man who built some of the greatest hotels in the world and has access to the best physicians. At the end of the workup, we found 2 brain aneurysms. He was in surgery a week later, and he was cured.

Those were ticking time bombs. It’s remarkable that his other doctors hadn’t found them.

We now have high-resolution imaging technology at our disposal. The cost has come down with the advent of AI, and the ability to interpret the images will improve.

Aneurysms are relatively easy to spot as long as you have the imaging study. If, for a relatively modest amount of money, you can ensure that you don’t have one of these ticking time bombs, it’s worth it.

Likewise, if the same imaging study can tell you whether you have a smoldering malignancy in your thyroid, kidney, pancreas, or brain, that’s enormously valuable.

How many of our friends were in perfect health, living the dream, when they found out they had subclinical kidney cancer? Fortunately, it’s easily addressed when you catch it early.

This isn’t new. The American Cancer Society said 30 or 40 years ago that early detection is the key to survival in cancer. The faster you find something, the more options you have to treat it. Excisional procedures for cancer can be lifesaving.

It also needs to be said that Dean Kamen and Martine Rothblatt are doing something extraordinary and almost magical, and you did a lot of the early work as well: regrowing or remanufacturing organs.

You can go from a stem cell—or even from a skin cell to a pluripotent stem cell using the Yamanaka factors—grow billions of those cells, differentiate them into a heart, liver, lung, or kidney, and remanufacture a brand-new organ with your own DNA and your own cell-surface antigens.

It’s the reason airplanes and Ford Model Ts from 100 years ago can still operate today: you can replace the parts.

I often tell families thinking about banking their children’s stem cells at birth, “If your baby were born with an extra set of kidneys, an extra set of lungs, and an extra heart, would you throw them out at birth?” That’s what you have when you store a supply of stem cells that can be used for these purposes.

I was the first person to take a solid organ and remove all the living cells from it.

What organ did you choose?

We originally started with the placenta, and we did it with hearts as well. We washed out all the cells—the living cells—from the organ, leaving behind a beautiful, 3D architectural template.

Let me give people a visual. If you have a heart and use a detergent, you can decellularize the heart—the cells fall away. What’s left is a massive collagen structure. It’s a combination of different structural proteins, but it’s basically the architecture of the organ.

It looks like a ghost organ. It’s translucent, almost like a glass cast of the actual heart. It has all the blood-vessel structures in place, as well as the mechanical structures, valves, and so on.

When I first did this with a placenta, I washed out all of the cells and then repopulated the organ in whatever way I wanted, based on the stem cells I implanted into it.

My original patent was entitled “Renovation and Repopulation of Cadaveric Organs and Tissue Matrices with Stem Cells.” It was the road map for what Martine and Dean are doing now.

They’re using that approach to create a repopulatable template and then using cells that are either fate-directed cells from induced pluripotent stem cells or donor cells.

Here’s the really cool thing: if you inject pluripotent, versatile stem cells into a perfectly preserved matrix of a tissue, they know where they are and differentiate appropriately.

GPS locations.

Exactly.

I want to wrap with a quick conversation about Celularity. People who look up your biography will see that you ran the cellular-medicine division at Celgene.

How big was Celgene?

We grew to about $120 billion in market capitalization at our peak.

Celgene was a remarkable place. It had the best people, the best leadership, and a science-driven, courageous culture. It was a great environment in which to be risk-tolerant and innovative.

At one point, we said it was a great environment, but you would thrive even more if we could spin out the cellular-medicine division. That became Celularity, which is now a public company under the symbol CELU.

You’ve built an extraordinary manufacturing facility in New Jersey, where you are right now. When you harvest a placenta—and I want to put LifeBankUSA in the show notes for anyone who wants to learn more—what do you do with the placenta once you receive it, and what products do you create?

The placenta is procured under very rigorous controls and transported under controlled logistics. In our laboratories, it’s processed to separate the cellular side of the organ from the tissue side.

From the tissue side, we make a whole range of surgical appliances. These products are used in wound healing, orthopedics, and ophthalmology. They use the natural architecture of the placental tissue to create replacements for skin, ligaments, tendons, cartilage, and more.

They’re increasingly popular as the basis for treating diabetic foot ulcers, venous stasis, burns, and other conditions.

The cells go on to be used to produce immune cells, pluripotent stem cells, and a whole range of other products. Celularity is a leading company in cellular and regenerative medicine, and we’re perfectly poised to deploy these therapies in the future of longevity therapeutics.

Bob, I’m grateful for you in my life. Thank you for the work that you’re doing. You’ve been an incredible scientist, CEO, engineer, and brother to me.

I hope people begin to understand the power that stem cells have. Stem cells are part of our regenerative toolkit and part of our future. We hear about adding decades of health to our lives; this is health-span extension.

We hear about epigenetic reprogramming, but another major area is cellular medicine and stem cells. We’ve even talked about supplementing the immune system with NK cells and T cells. We’ll leave that for another episode.

I love you, brother, and thank you, as always, for our time together.

I love you, too. Thanks so much for having me. You’re the inspiration that got us here, so keep it up.