Speaker 1: Pushkin. When the war in Ukraine broke out a few
Speaker 1: years ago, Laura Nicholson started hearing from Ukrainian doctors who
Speaker 1: were treating soldiers at frontline hospitals.
Speaker 2: When patients would present to the hospital. In many cases,
Speaker 2: these were soldiers who had been injured in the war,
Speaker 2: typically with blast injuries and shrapnel injuries, because you know,
Speaker 2: ied explosions are really one of the you know, that's
Speaker 2: modern warfare. People lose limbs, and one of the reasons
Speaker 2: they lose limbs is because the blood flow gets damaged
Speaker 2: and cut off, and it's very hard to restore that
Speaker 2: blood flow, especially since the wounds are very contaminated. That
Speaker 2: these these limbs are filled with shrapnel and metal and soil,
Speaker 2: and it's just it's very horrific.
Speaker 1: In some cases, the doctors were getting in touch with
Speaker 1: Laura because she and her colleagues had spent more than
Speaker 1: twenty years figuring out how to use human cells to
Speaker 1: create new blood vessels outside the human body. The idea
Speaker 1: is to create a supply of vessels that surgeons can
Speaker 1: have on hand to implant into patients. She calls these
Speaker 1: vessels havs, or human acellular vessels. The havs have not
Speaker 1: yet been approved by the FDA, but the Ukrainian surgeons
Speaker 1: thought they would be helpful, so after getting approval from
Speaker 1: the Ukrainian Ministry of Health, Laura and her colleagues sent
Speaker 1: havs to several frontline hospitals in Ukraine.
Speaker 2: So when these patients would present to the hospital, if
Speaker 2: the surgeon felt that the best treatment for that patient
Speaker 2: was using the engineered vessel to rapidly restore blood flow,
Speaker 2: he would do that. And so that means, you know,
Speaker 2: cleaning out the wound. You know, the patients asleep at
Speaker 2: this time, and they're having other injuries fixed as well,
Speaker 2: but cleaning out the wound, isolating the damaged artery and
Speaker 2: then replacing the damage segment with our engineered vessel.
Speaker 1: And how did it go?
Speaker 2: Well? The outcomes in Ukraine went very well. We treated
Speaker 2: a total of nineteen patients over a year long humanitarian effort,
Speaker 2: and in fact we're still following those patients now. But
Speaker 2: what we found is that in the first month, which
Speaker 2: is really the most important time after somebody gets injured,
Speaker 2: it's how things go in the first month. What we
Speaker 2: found in the first month is that of the nineteen
Speaker 2: patients we treated. Every single limb was salvaged. There was
Speaker 2: no loss of limb, there was no loss of life.
Speaker 2: And this is true even though some of the patients
Speaker 2: we treated were very badly injured. And in fact, one
Speaker 2: of the patients, the surgeon told us later that he
Speaker 2: was quite sure this man would die, but he survived
Speaker 2: and he walked out of the hospital on his own leg.
Speaker 2: So I believe in my heart that there are soldiers
Speaker 2: in Ukraine who are walking and breathing now who would
Speaker 2: not be if it weren't for the AHAV.
Speaker 1: I'm Jacob Goldstein and this is What's Your Problem, the
Speaker 1: show where I talk to people who are trying to
Speaker 1: make technological progress. My guest today is Laura Nicholson. She's
Speaker 1: the co founder and CEO of Humo site. Laura's problem
Speaker 1: is this, can you use human cells to create a
Speaker 1: blood vessel that is better, at least for some patients
Speaker 1: than any other options available today. Laura has both a
Speaker 1: PhD and an MD. She's worked as a physician in
Speaker 1: the intensive care unit. So to start, I asked her
Speaker 1: how she got into the blood vessel business in the
Speaker 1: first place.
Speaker 2: Well, you know, I started working trying to grow arteries
Speaker 2: from scratch. In the mid nineteen nineties, I was training
Speaker 2: for my residency at mass General Hospital. I was taking
Speaker 2: care of patients in the operating room. I was an
Speaker 2: antithesiologist and an intensive care unit doctor, and I took
Speaker 2: care of a lot of patients who had vascular disease
Speaker 2: in their heart or their legs or elsewhere. And you know,
Speaker 2: diseases of arteries are still the biggest killers of people
Speaker 2: in the Western world, more so than cancer, more so
Speaker 2: than anything else.
Speaker 1: Right, Sometimes we call it heart disease, right, but it's
Speaker 1: cardiovascular disease. And the vascular piece there is vessels, right.
Speaker 2: Yes, So it can be any artery supplying any part
Speaker 2: of your body, and when those fail or clot or
Speaker 2: dilate or become infected, they need to be bypassed or replaced.
Speaker 2: And it's a universal thing in all of healthcare. And
Speaker 2: what I learned during my training is that typically when
Speaker 2: we need to repair or replace an artery, we rob
Speaker 2: Peter to pay Paul. In other words, we cut open
Speaker 2: one part of your body and take a vein out
Speaker 2: or an artery out, and then we move it over
Speaker 2: and use that vein or artery to repair the artery
Speaker 2: that's broken.
Speaker 1: Like the classic as somebody's getting a bypass surgery for
Speaker 1: the blood vessels around their heart, and the surgeon takes
Speaker 1: vessels from their leg, right, you take vessels from the
Speaker 1: thid and you put it next to the heart.
Speaker 2: Yes, yes, And as you might imagine, that always injures
Speaker 2: the patient in the process of trying to fix the patient.
Speaker 2: But importantly, not everybody has veins and arteries hanging around
Speaker 2: in their body that are spare, that are the right
Speaker 2: quality and the right size and shape to fix the
Speaker 2: problem at hand. And when that happens, surgeons are forced
Speaker 2: to use plastic tubes, tubes made out of teflon, for example.
Speaker 2: And as you might imagine, if you sew a teflon
Speaker 2: tube into your vein ascular system, that often doesn't work
Speaker 2: very well. It clots, it gets infected, it can be problematic.
Speaker 2: So so I became really interested during my training thirty
Speaker 2: years ago in whether or not we could make new
Speaker 2: arteries for patients that would behave like their own veins
Speaker 2: and arteries, but whether we could we could manufacture them,
Speaker 2: you know, make basically spare parts that would be available
Speaker 2: off the shelf.
Speaker 1: How how is that idea received at that time, so.
Speaker 2: People people viewed it as very much like science fiction,
Speaker 2: but also maybe not in a good way. So some
Speaker 2: some of my some of even my close friends, when
Speaker 2: I started working on this, they kind of stepped back
Speaker 2: and looked at me funny, like, are you really serious here?
Speaker 2: Is this something you're really going to try to do?
Speaker 2: You know, grow an artery in a jar? You know,
Speaker 2: nobody will take you seriously if you try to do that. So, yes,
Speaker 2: that was absolutely the vibe in the nineteen nineties.
Speaker 1: So you're a medical resident, your physician, learning you know,
Speaker 1: the clinical skills you need to be a practicing physician.
Speaker 1: Then you get this idea, you want to grow blood
Speaker 1: vessels in a jar. How do you even do that? Like,
Speaker 1: they're not doing that at Mass General.
Speaker 2: Yeah, so the idea of wanting to grow a vessel
Speaker 2: in a jar, You're right, it's not an obvious idea
Speaker 2: that pops into somebody's head. But I was fortunate enough
Speaker 2: to be able to work in the laboratory of Robert Langer,
Speaker 2: who's still a very accomplished investigator, one of the most
Speaker 2: famous investigators at MIT. And as you may know, MIT
Speaker 2: is right across the river from mass General where I
Speaker 2: was doing my residency, and Langer's lab was really one
Speaker 2: of the pioneers in developing this whole concept of tissue engineering,
Speaker 2: basically growing tissues from scratch. So I developed this sort
Speaker 2: of hybrid identity where I would do my clinical training
Speaker 2: during the day at mass General, and then after I
Speaker 2: was done with my cases, I take the subway and
Speaker 2: go across the river and then work in Langer's lab
Speaker 2: in the afternoon and evening and try to figure out
Speaker 2: how you grow an artery and a jar. So I
Speaker 2: got very excited about this and joined his lab in
Speaker 2: ninety five and worked for about three and a half years,
Speaker 2: and then was able to demonstrate and publish really the
Speaker 2: first functional engineered artery in a large animal. We published
Speaker 2: that in nineteen ninety nine, where I took cells from
Speaker 2: pigs and grew arteries for those pigs and then implanted
Speaker 2: them back and they worked, and we published that in
Speaker 2: Science and at the time that made quite a splash.
Speaker 1: So what was the state of tissue engineering more generally
Speaker 1: at that time people do at that time?
Speaker 2: Well, the state of tissue engineering in the nineteen nineties
Speaker 2: was really there had been some successes in what I
Speaker 2: would call sort of simpler connective tissues. So just to
Speaker 2: step back a little bit, our bodies are divided into
Speaker 2: connective tissues and non connective or organ tissues. And connective
Speaker 2: tissues are any tissues that hook one part of the
Speaker 2: body to the other, so that's skin, bone, blood, vessel, tendon,
Speaker 2: what have you. And then organs are obviously heart, liver, kidney,
Speaker 2: stuff like that. So there had been some successes even
Speaker 2: in the nineteen nineties in growing engineered tissues, for example,
Speaker 2: skin and cartilage, and in fact, engineered skin and cartilage
Speaker 2: by the mid to late nineteen nineties were already on
Speaker 2: the market, they were being used in patients, and so
Speaker 2: the early feasibility with some simpler connective tissues had really
Speaker 2: already been demonstrated by that time.
Speaker 1: So, okay, this is whatever twenty five ish years ago.
Speaker 1: Just at the end of last year, at the end
Speaker 1: of twenty twenty three, you applied for FDA approval. You're
Speaker 1: likely to hear back in the next few months. So
Speaker 1: what were a few of the things you had to
Speaker 1: figure out to get from where you were twenty five
Speaker 1: years ago to where you are now.
Speaker 2: So it has been a long journey. Initially we thought, oh, well,
Speaker 2: we'll take a small biopsy from a patient who needs
Speaker 2: an artery and will grow their cells, and then we'll
Speaker 2: make that patient a new artery and then give it
Speaker 2: back to them.
Speaker 1: So it's custom, it's bespoke.
Speaker 2: It was bespoke tissue engineering. The problem with that, though,
Speaker 2: is twofold one. It takes a long time. Yes, so
Speaker 2: if you're a patient with chest pain or.
Speaker 1: Who just got blown up by an IED, or who
Speaker 1: just got.
Speaker 2: Blown up by an IED, you don't really have three
Speaker 2: or four months to wait around for a new art
Speaker 2: So that's fundamentally a problem. But also what we found,
Speaker 2: and this was during some work that I did while
Speaker 2: I was still in academia at Duke University, what we
Speaker 2: found is that for older patients who have vascular disease,
Speaker 2: if we try to take those cells from those patients
Speaker 2: and grow new arteries for those patients, it actually doesn't
Speaker 2: work very well. You know, their vessels are old and
Speaker 2: their cells are old. And we found that and publish that,
Speaker 2: and we have a whole series of papers on that.
Speaker 2: But that really led us to a fundamental pivot, which
Speaker 2: was the insight that we could use young, healthy cells
Speaker 2: from humans, use those to grow arteries. But then after
Speaker 2: we grew the arteries from scratch, we would wash the
Speaker 2: cells out of the engineer tissue. And what that leaves
Speaker 2: behind is extracellular matrix, which can then be implanted into anybody.
Speaker 1: I mean, that's essentially where you arrived and what you
Speaker 1: are doing now, right, And so I want to talk
Speaker 1: about that in a little more detail. Basically, how it works,
Speaker 1: how you make the thing that you make. So where
Speaker 1: do you start.
Speaker 2: So we start with human cells and the cells that
Speaker 2: we use. So right now human site has banks of
Speaker 2: human cells, and in fact, we have enough cells banked
Speaker 2: to support tissue production for the next thirty or forty years.
Speaker 2: We've got a lot of cells. But where those cells
Speaker 2: come from is actually they come from organ and tissue donors.
Speaker 2: So if a patient dies and they become an organ donor,
Speaker 2: their heart might go somewhere and their liver might go
Speaker 2: somewhere else, but there's actually no transplantation use for their
Speaker 2: blood vessels. So we worked with organ procurement organizations and
Speaker 2: we obtained consent from donor families, and we obtained large
Speaker 2: blood vessels aortas from hundreds of different organ donors. We
Speaker 2: isolated cells from those donors, and then we did a
Speaker 2: tremendous amount of screening to identify which cells would really
Speaker 2: be optimal for growing new arteries, and then we established banks.
Speaker 2: So actually we have banks of donor cells now that
Speaker 2: are derived from organ donors.
Speaker 1: So it's like vials of cells in fluid in the
Speaker 1: refrigerator or something like that.
Speaker 2: It's vials of cells stored in liquid nitrogen, so they're
Speaker 2: extremely cold, but that means that the cells can store
Speaker 2: for decades.
Speaker 1: Okay, so very good. That's step one. Get a lot
Speaker 1: of nice, healthy or to cells. And just to be clear,
Speaker 1: by the way, that our blood vessel cells the same
Speaker 1: in all of the vessels. Dumb question, But are the
Speaker 1: cells of the order the same as the cells in
Speaker 1: whatever other blood vessel.
Speaker 2: The cells even within your aorta, there's different flavors of cells,
Speaker 2: and the cells differ between arteries and veins and big
Speaker 2: arteries and small arteries and capillaries. So that was really
Speaker 2: part of the challenge for us, was really identifying which
Speaker 2: subset of cells in the aortas was really the most
Speaker 2: productive for growing new arteries. As it turns out, some
Speaker 2: of the cells in your body, even if you're an
Speaker 2: older person still have this sort of progenitor or stem
Speaker 2: like capability. And those cells we found could grow extensively
Speaker 2: in our process and could grow large numbers of new arteries.
Speaker 1: Great, so you got not only a lot of cells,
Speaker 1: you got a lot of the right kind of cells.
Speaker 2: What do you do with them? Well, when we want
Speaker 2: to grow a batch of arteries. Right now, we grow
Speaker 2: two hundred arteries at a time in a highly automated
Speaker 2: system that we've designed and built over many years.
Speaker 1: Artery factory.
Speaker 2: It's an artery factory, yes, yes, In fact, we have
Speaker 2: eight installed units now. Each unit, which we call a
Speaker 2: Luna two hundred unit, can grow two hundred vessels at
Speaker 2: a time.
Speaker 1: A unit is like a machine.
Speaker 2: It's a machine. It's a machine. It's about as big
Speaker 2: as a school bus, and it's essentially a large incubator
Speaker 2: where we control temperature and humidity and oxygen. But we
Speaker 2: also have inside the school bus, inside the incubator, we
Speaker 2: have bioreactor systems where where we can provide an environment
Speaker 2: for the cells while they're growing, so that the cells
Speaker 2: form new arteries. But I'm sort of jumping ahead a
Speaker 2: little bit. So when we start a batch, what we
Speaker 2: do is we take a tiny vial of cells. It's
Speaker 2: about a fifth of a tea spoon. It's a little
Speaker 2: tiny volume, and we thaw out those cells and then
Speaker 2: we grow them and we let them expand about two thousandfold,
Speaker 2: and then we take we gather all those cells and
Speaker 2: then we essentially walk over to one of our production units,
Speaker 2: one of our Luna two hundreds, and in the Luna
Speaker 2: two hundred is two hundred what we call bioreactor bags.
Speaker 2: Each bag has a has a scaffold inside of it
Speaker 2: that's sterile. And that scaffold is six millimeters in diameter
Speaker 2: and forty centimeters long, So that's the size of the
Speaker 2: artery we grow.
Speaker 1: So and it's made of like plastic or something.
Speaker 2: It's a degradable it's a degradable plastic. It's actually it's
Speaker 2: the same material that's used in degradable sutures. So each
Speaker 2: fiber is about the width of a cell, and there's
Speaker 2: a lot of empty space in between the fibers. But
Speaker 2: this this the shape of the scaffold. We can we
Speaker 2: can shape it into this six millimeter diameter tube that's
Speaker 2: forty centimeters long. And what we do is we take
Speaker 2: the cells that we grow, and we inject them into
Speaker 2: the bag and the cells stick onto the stick, stick
Speaker 2: onto the fibers of the scaffold. It's like a person.
Speaker 2: It's like a person hanging onto a metal pole on
Speaker 2: building scaffolding. If you think of it that, that's kind
Speaker 2: of what it's like.
Speaker 1: And so the cells are grabbing sort of all over
Speaker 1: this little plastic tube, all over the scalfeld.
Speaker 2: Yes, each cell grabs onto a metal pole and they
Speaker 2: hang on for dear life. And then then we basically
Speaker 2: fill the bag, the bioreactor bag, with culture medium. And
Speaker 2: then that culture medium is super secret. It has lots
Speaker 2: of yummy stuff in it that convinces the cells to
Speaker 2: grow and to while they're growing, they secrete proteins like
Speaker 2: collagen and other matrix molecules. What also happens while while
Speaker 2: the cells are growing in the culture medium is we've
Speaker 2: just sign the bioreactor bag so that we can stretch
Speaker 2: the cells as if as if the cells are in
Speaker 2: the wall of an artery and they're feeling your heart beat.
Speaker 1: Huh, because because arteries need to get wider and get
Speaker 1: narrow as the pulse of blood comes in and out. Yes, yes,
Speaker 1: so if you well, there's two different numbers in your
Speaker 1: blood pressure reading exactly.
Speaker 2: There's a there's a higher pressure in a lower pressure.
Speaker 2: And if you put your if you put your finger
Speaker 2: on your wrist, you can feel your pulse. That pulse
Speaker 2: is your artery distending and then and then recoiling every
Speaker 2: time your heart beats. Well, it turns out we learned
Speaker 2: very early. We figured out when I was working in
Speaker 2: Langer's lab in the nineties that if we didn't stretch
Speaker 2: these cells while they were growing, they didn't really make
Speaker 2: an artery because they didn't know they were supposed.
Speaker 1: To do that. So they would be too like rigid,
Speaker 1: they wouldn't be able to.
Speaker 2: They would be pul they would be disorganized. Actually, they
Speaker 2: would just grow randomly because they didn't know what they
Speaker 2: were supposed to be doing.
Speaker 1: Huh. So it's like that that pulse kind of it
Speaker 1: tells them how to grow and organize themselves. That's really interesting.
Speaker 2: It's really interesting.
Speaker 1: Yeah, So so you do that in the bag? How
Speaker 1: do you get them to so you have a little
Speaker 1: sort of imitation heartbeat sort of in the bag.
Speaker 2: We have a little imitation heartbeat in the bag, Yes,
Speaker 2: and every vessel gets stretched the same amount, and they
Speaker 2: get stretched cyclically by this heartbeat for the entire two
Speaker 2: month culture duration.
Speaker 1: So they spend two months growing and learning how to
Speaker 1: be cells in an artery and filling in all the
Speaker 1: spaces on the scaffold on the little plastic tube. What
Speaker 1: happens at the end of that two months, well, at.
Speaker 2: The end of the two months, a couple things have happened.
Speaker 2: One is that that scaffolding, which I said is degradable,
Speaker 2: has mostly degraded, so it's like it's pretty much all gone.
Speaker 2: So what we have by that time is a human
Speaker 2: artery that has these cells and also the collagen matrix
Speaker 2: proteins that they made, and there's really no scaffold left.
Speaker 2: Huh So in a final step, we re drain out
Speaker 2: the culture medium that we use to convince the cells
Speaker 2: to grow, and then we replace it with detergents and
Speaker 2: we basically we spend five days and we washed the
Speaker 2: cells out of the artery.
Speaker 1: Huh So, So after two months, when you take it out,
Speaker 1: it feels like it's a lot like an artery in
Speaker 1: my body, in your body, in anybody's body. But that's
Speaker 1: not good because if you put that in a patient,
Speaker 1: you'll have an immune a bad immune response. That's presumably
Speaker 1: the problem. Why you can't just use that.
Speaker 2: That's the reason, yes, because again these are these are
Speaker 2: cells from a cell bank. So if I if I
Speaker 2: grow that artery and then I implanted in you, your
Speaker 2: body will reject it because.
Speaker 1: It's certainly I'm getting a transplant. And so what is
Speaker 1: what is that final step or that that next step?
Speaker 2: So the final step we call that decellularization. So we
Speaker 2: rinse away the cells, which are really the part that
Speaker 2: creates the immune rejection. But what we leave behind, and
Speaker 2: what we're very careful not to disturb, is the extracellular
Speaker 2: matrix proteins like the collagen that I mentioned, there's actually
Speaker 2: forty or fifty proteins there. The reason that's important is
Speaker 2: because it's really the collagen and the proteins that give
Speaker 2: the vessel all of its mechanical properties. So actually washing
Speaker 2: the cells out of the tissue doesn't change how strong
Speaker 2: it is. It's still just as strong as your arteries.
Speaker 2: After we wash the cells out, the cells are really
Speaker 2: there to be little protein factories, yeah right, but they
Speaker 2: themselves are not very strong.
Speaker 1: Huh So.
Speaker 2: But because collagen is so important, like for example, your
Speaker 2: collagen and my collagen are identical. Huh, they're identical.
Speaker 1: You're saying, there's no kind of there's no potential immune response.
Speaker 1: It's just protein. It's just these exact same protein. You
Speaker 1: couldn't tell the difference, Yes, you couldn't tell who it came.
Speaker 2: Your body, Yes, your body can't tell the difference. And
Speaker 2: so we've implanted these decellularized, engineered arteries into nearly six
Speaker 2: hundred patients over the last eleven years. We've never seen
Speaker 2: a single episode of rejection.
Speaker 1: Because in an immune sense, there's nothing to reject.
Speaker 2: That's what we believe.
Speaker 1: Yes, so now it's like kind of like a dead artery,
Speaker 1: an artery without any personality, a generic artery. You put
Speaker 1: it in a person and a patient.
Speaker 2: What happens then, well, there's a couple things that happened.
Speaker 2: The first thing that happens is that the artery works
Speaker 2: as it should. So the main job of arteries is
Speaker 2: to conduct blood flow so that you can get blood
Speaker 2: from point A to point B. So that happens as
Speaker 2: soon as the surgeon sews it in and takes the
Speaker 2: clamps off. So some people worry, g we wash the
Speaker 2: cells out, will.
Speaker 1: It be leaky.
Speaker 2: That doesn't happen. We don't see that. But what's probably
Speaker 2: cooler is that over time, sells from the patient see
Speaker 2: this naked artery and to them it sort of looks
Speaker 2: like an empty apartment building. And what we've seen happen,
Speaker 2: in fact we've published this, is that cells from the
Speaker 2: patient migrate into the acellular artery and they start off
Speaker 2: being progenitor cells, but they become vascular cells. So over
Speaker 2: a period of months, this non living thing becomes a
Speaker 2: living artery and it's the patient's own. So this is really,
Speaker 2: I think this is regenerative medicine in the truest sense.
Speaker 1: Can you tell the difference whatever a year later, between
Speaker 1: the section of artery that you put in and the
Speaker 1: patient's own artery.
Speaker 2: You can tell differences. There are still subtle differences. There
Speaker 2: is one there's one stretchy protein called elastin, which is
Speaker 2: in all of our arteries, but are the engineered arteries
Speaker 2: don't have elastin, So that's actually the easiest way to tell.
Speaker 2: Aside from that, there's not a lot of differences.
Speaker 1: Does the absence of elastin make a functional difference?
Speaker 2: It doesn't seem to. This is something that I used
Speaker 2: to worry about as a younger professor ten, fifteen, twenty
Speaker 2: years ago, but over a thousand patient years of exposure
Speaker 2: tells us that it probably doesn't matter.
Speaker 1: It's weird that there's a thing in our arteries that
Speaker 1: we could do without. You'd think that, would you know?
Speaker 1: I like the way you know fish that live in
Speaker 1: caves for a million years don't have eyes anymore because
Speaker 1: it's costly to have eyes, and if you don't need
Speaker 1: they evolve away.
Speaker 2: Well, I think that's the difference between having no elastin
Speaker 2: in your body, but having or not having elastin just
Speaker 2: in a short segment. So if you have no elastin
Speaker 2: in your whole body, that's actually that makes life very
Speaker 2: very hard for your heart. However, if it's just a
Speaker 2: short segment of the vessels in your body that don't
Speaker 2: have elastin, your heart doesn't care too much.
Speaker 1: We'll be back in a minute. Laura's company, Humocite, applied
Speaker 1: late last year for FDA approval. They expect to hear
Speaker 1: back this summer, and she told me about the evidence
Speaker 1: that made her think that made the company think that
Speaker 1: they were finally ready to apply for FDA approval. For
Speaker 1: widespread use of these vessels they're creating.
Speaker 2: So the trial that is supporting our current application at
Speaker 2: the FDA was conducted at nineteen trauma centers in the
Speaker 2: US and Israel, and we treated a total of seventy
Speaker 2: patients who had all sorts of injuries, you know, car accidents,
Speaker 2: gunshot wounds, industrial accidents. We treated a guy who worked
Speaker 2: on a farm who was crushed by a cow, We
Speaker 2: treated a woman who was crushed by a crane on
Speaker 2: a dock. I mean, just all sorts of terrible injuries.
Speaker 2: And then we followed those patients, many of them were
Speaker 2: still following, But it was really the data from that
Speaker 2: pivotal trial that showed really excellent outcomes in terms of safety,
Speaker 2: but also in terms of how well blood flow was
Speaker 2: restored and a very low number of amputations and infections.
Speaker 2: So seeing all of that clinical data together from this
Speaker 2: pivotal trial and then combined with the Ukraine exit experience,
Speaker 2: because the Ukraine humanitarian effort was ongoing at the same
Speaker 2: time we were doing this pivotal trial, So putting all
Speaker 2: of that information together is what really formed the basis
Speaker 2: of our filing with the FDA. Last year.
Speaker 1: You mentioned that there are other options. Where do your
Speaker 1: arteries fit in this sort of you know, comparative landscape,
Speaker 1: like when is something else better? And when is one
Speaker 1: of your arteries better?
Speaker 2: Well, this is something that you know the FDA would
Speaker 2: argue is probably their decision to make. Our argument is
Speaker 2: that in patients who don't have their own vein available,
Speaker 2: and for injured patients, it may be because their limbs
Speaker 2: are injured. It may be because the need to restore
Speaker 2: blood flow is so acute that the surgeons don't don't
Speaker 2: have that extra hour to harvest the vein. It could
Speaker 2: be that the surgeon doesn't want to injure the patient.
Speaker 2: Further so, in patients in whom vein is not feed
Speaker 2: our argument is that the hav is an excellent option.
Speaker 2: And our data showed when we compared our outcomes to
Speaker 2: outcomes of patients who are treated with plastic graphs like
Speaker 2: made out of teflon in trauma, our data showed that
Speaker 2: our outcomes are substantially better than plastic graphs.
Speaker 1: What are some of the next things that you're working on,
Speaker 1: Like what are you trying to figure out now?
Speaker 2: Well, on the clinical side, we have trials that are
Speaker 2: under ways that we're still collecting data on in patients
Speaker 2: with kidney failure who we're studying our engineered vessels as
Speaker 2: what we call a dialysis access, which is where our
Speaker 2: vessels are sown into the patient's arm between an artery
Speaker 2: and a vein, and then that vessel is used in
Speaker 2: the dialysis clinic where nurses poke needles into the vessel
Speaker 2: and use that so the patient can get dialysis. So
Speaker 2: we're studying that indication, and in fact, we have another
Speaker 2: pivotal trial that we expect to read out in the
Speaker 2: third quarter of this year in twenty twenty four that
Speaker 2: will tell us if the HAV works better in dialysis
Speaker 2: then basically the gold standard, which is where a surgeon
Speaker 2: sows an artery in a vein together directly.
Speaker 1: So that's the kind of short term future. It's basically
Speaker 1: trying to trying to get the dialysis related indication. When
Speaker 1: you think more long term, if you think, I don't
Speaker 1: even know how many years that is for you, Is
Speaker 1: it five years, is it ten years?
Speaker 2: Like?
Speaker 1: What do you think about?
Speaker 2: So for the last several years, we've been making smaller
Speaker 2: diameter vessels that are the right size for hard bypass,
Speaker 2: and we've actually been testing these three and a half
Speaker 2: millimeter vessels doing heart bypasses in primates, non human primates,
Speaker 2: and other large animals. And we're collecting a long term
Speaker 2: data to submit as a file to the FDA in
Speaker 2: order to gain approval to do a phase one trial
Speaker 2: in patients who need a heart bypass but who don't
Speaker 2: have their own vein to do the bypass. So we
Speaker 2: would hope to start that first in human trial in
Speaker 2: heart bypass in the next couple of years.
Speaker 1: So bypass is a unfortunately wildly common procedure. My dad
Speaker 1: had one, my grandfather had a few, taking statins and
Speaker 1: running all the time and hopes that I'll dodge that bullet.
Speaker 1: But who knows. So presumably that would be a very
Speaker 1: large market. I mean, it's also the case that many
Speaker 1: patients are able to use their own veins. You mentioned
Speaker 1: you're thinking about patients who can't in what instances are
Speaker 1: graphs unavailable for patients getting bypassed and what do doctors
Speaker 1: now in those instances.
Speaker 2: Well, there's lots of situations where patients who need a
Speaker 2: vein for hard bypass don't have it. So, for example,
Speaker 2: if you have varicose veins, if your veins are very dilated.
Speaker 2: Surgeons can't use them in the modern area era vein
Speaker 2: clinics are sclerosing people's veins all the time so that
Speaker 2: ladies can have beautiful legs at the beach, which is
Speaker 2: great in the short term, but not so good in
Speaker 2: the long term. And then lastly, as we know, there's
Speaker 2: a growing obesity and diabetes epidemic in the United States
Speaker 2: most of the western world. For those patients, if you
Speaker 2: cut into their legs and take their vein out, they
Speaker 2: have a higher rate of complications. Their incisions don't heal,
Speaker 2: they get infected, they have all sorts of problems.
Speaker 1: Are there not teflon artificial veins that can be used
Speaker 1: for bypass?
Speaker 2: There's nothing artificial that works for those small diameter vessels
Speaker 2: in your heart, despite a huge need, there simply isn't anything.
Speaker 1: So you said that when you started out, you know,
Speaker 1: twenty five thirty years ago, making connective tissue like blood vessels,
Speaker 1: like what you're doing, seemed much easier than making solid organs.
Speaker 1: And so I'm curious, after all this time and all
Speaker 1: the advancements there have been, does making a solid organ
Speaker 1: in a lab still feel you know, wild hard it's.
Speaker 2: Still wild, hard, but it's starting to feel tractable. So
Speaker 2: one of the parts that we haven't talked about is,
Speaker 2: you know, I've had this dual life for many years
Speaker 2: as a Right now I'm the CEO of Humusite, and
Speaker 2: I'm not an academic anymore. But for many years I
Speaker 2: sort of had one foot in academia and one foot
Speaker 2: in my company. And while I was working as a
Speaker 2: professor at Yale, we were the first lab to actually
Speaker 2: be able to grow engineered lung and implant them in
Speaker 2: rats and showed that they could exchange gas for a
Speaker 2: few hours. So we have a pathway I believe to
Speaker 2: growing more complex tissues, lungs in particular, And in fact,
Speaker 2: some of my former trainees from my labors are off
Speaker 2: scattered at different institutions working on that problem.
Speaker 1: Right now on lab grown lungs. In lab grown lungs
Speaker 1: are lungs less complex than other organs? Is that why lungs?
Speaker 2: Lungs are not less complex, but lungs, Interestingly, they're the
Speaker 2: only organ in your body that's mostly empty space. And
Speaker 2: in biology, in biotechnology, we're very good at growing thin
Speaker 2: layers of cells or monolayers or thin collections of cells.
Speaker 2: One of the things that we did figure out in
Speaker 2: my academic lab is that instead of using a plastic
Speaker 2: scaffold for lungs, what we can probably do is take
Speaker 2: a native lung, either a human lung or maybe a
Speaker 2: primate lung or a pig lung and decellularize that lung
Speaker 2: and use that as a scaffold. In that case, we
Speaker 2: could maybe take stem cells from the patient and repopulate
Speaker 2: that scaffold that has all of the structure of the lung,
Speaker 2: all the air sacs, all the blood vessels, all of
Speaker 2: that important lung structure. If we can repopulate that with cells,
Speaker 2: then we're basically we kind of have a leg up.
Speaker 2: We've got the lung structure to start with, and then
Speaker 2: we just repopulate it with cells from the patient, and
Speaker 2: then we've got a designer organ.
Speaker 1: We'll be back in a minute with the Lightning Round.
Speaker 1: So I'm cognizant of the time. I just want to
Speaker 1: ask you some Lightning Round questions to finish.
Speaker 2: That.
Speaker 1: They will be slightly more random than the questions I've
Speaker 1: asked you so far. What's one thing you learned from
Speaker 1: Bob Langer.
Speaker 2: I learned from Bob Langer that time is the one
Speaker 2: thing you can't get back that things cost. Getting things
Speaker 2: done cost effort, and they cost money, and they cost time.
Speaker 2: You can get more effort, and you can get more money,
Speaker 2: but you can't get more time. So he was always
Speaker 2: focused on finding the most efficient way to get something
Speaker 2: done that took the least amount of time, because, as
Speaker 2: it turns out, everything takes longer than you think it's gonna.
Speaker 1: It's interesting to think about him that way, right because
Speaker 1: I interviewed him and I was like, how did you
Speaker 1: do so many things? And he I don't know if
Speaker 1: he knew, but like that answer that you just gave
Speaker 1: is a pretty good answer for how he did so
Speaker 1: many things. So it was what the mid nineties is
Speaker 1: that right when you started sort of getting into regenerative medicine,
Speaker 1: And I'm curious, you know, that's thirty years ago now,
Speaker 1: and I'm curious looking back now, it's sort of what
Speaker 1: you thought then. What is something that's progressed more quickly
Speaker 1: than you thought it would?
Speaker 2: Tools tools one of the reasons that sell therapy and
Speaker 2: regenerative medicine is taking off now and we'll continue to
Speaker 2: just explode in the next couple decades is tools. We
Speaker 2: can look at a tissue that we're growing and sort
Speaker 2: of gate generate sort of a report card of here's
Speaker 2: how the cells are behaving. You know, fifteen percent of
Speaker 2: the cells are behaving correctly, eighty five percent of the
Speaker 2: cells are not doing what they're supposed to do. And
Speaker 2: I can compare that report card to what a native
Speaker 2: tissue looks like, and then I can go back and
Speaker 2: fix what I'm doing on the engineered side and just
Speaker 2: iterate that way, it allows you to make a roadmap.
Speaker 1: What's something that has progressed more slowly than you would
Speaker 1: have thought.
Speaker 2: I think that. I think that the development of functional
Speaker 2: connective tissues has progressed more slowly than I would have thought.
Speaker 2: The thing you do, the thing I do, the thing
Speaker 2: I do, and I'm surprised at that if we look
Speaker 2: at so as I said, in the nineteen nineties, there
Speaker 2: were approved versions of tissue engineered cartilage and tissue engineered
Speaker 2: skin that were on the market in the US or Europe.
Speaker 1: Did those just turn out to be way easier than
Speaker 1: everything else?
Speaker 2: Or what they are? They're easier, the tissues are simpler,
Speaker 2: and the what we would say to our design requirements
Speaker 2: are a little bit less stringent. So what has progressed
Speaker 2: more slowly than I would have thought is making tissues
Speaker 2: that have tougher design criteria and doing that successfully.
Speaker 1: Seems like you're almost there, We're.
Speaker 2: Almost there, But it does I've been working on it
Speaker 2: for thirty years. It does take time.
Speaker 1: Did you feel like you were almost there ten years ago.
Speaker 2: I felt like I was almost there twenty years ago.
Speaker 1: But this time you mean it?
Speaker 2: This time, I mean it? But no, I think you know.
Speaker 2: I think it's to make tissues, you have to understand
Speaker 2: the cell biology and that single cell information that I mentioned,
Speaker 2: But you also really have to come to grips with
Speaker 2: what the tissue does and what characteristics the whole tissue
Speaker 2: must have in order to function. And that's a complicated
Speaker 2: set of problems, and it takes it. You know, one
Speaker 2: person can't do it all. It takes a really terrific
Speaker 2: team working on it for a long time.
Speaker 1: Do you think that having a founding team that was
Speaker 1: all women affected the culture of the company.
Speaker 2: It affected a lot of things. It affected the culture
Speaker 2: of the company. Humo site has never suffered from a
Speaker 2: sense that women can't be heard in a meeting. It's
Speaker 2: actually allowed us to attract and retain incredibly smart and
Speaker 2: high powered women because they know they will never have
Speaker 2: to fight that uphill battle. So it actually gives us
Speaker 2: an edge in terms of recruitment. But in retrospect, now
Speaker 2: having been at this for nearly twenty years, I would
Speaker 2: say that in the early years, I think it made
Speaker 2: it harder for us to raise money. People write about this,
Speaker 2: and people used to ask me about it early on,
Speaker 2: and I sort of discarded it as being paranoid. But
Speaker 2: now looking back, I think it hurt us. I just
Speaker 2: think that people there's an expectation that, well, if this
Speaker 2: is an all woman company, then you know, maybe this
Speaker 2: isn't going to work.
Speaker 1: What's one thing you wish more people understood about cells?
Speaker 2: I wish that people appreciated how smart cells are. What
Speaker 2: do you mean, Well, what I've learned is that if
Speaker 2: I work with the right starting cells, if I give
Speaker 2: them about eight cues, not one que, but it's not
Speaker 2: a thousand ques. If I give them about eight cues,
Speaker 2: a couple of the right growth factors, right amount of stretch,
Speaker 2: you know, right temperature, right oxygen level. If I give
Speaker 2: them about eight cues, they take it and run with it,
Speaker 2: and without any supervision for me, they make a brand
Speaker 2: new artery that looks and feels like the real thing.
Speaker 2: And that's a remarkable amount of intelligence inside a little
Speaker 2: tiny cell. So our cells are very self directed, they're
Speaker 2: very smart, and in order to coax them to make
Speaker 2: spare parts, we just have to figure out what that
Speaker 2: right handful of cues is.
Speaker 1: Laura Nicholson is the co founder and CEO of Humo site.
Speaker 1: Today's show was produced by Gabriel Hunter Chang. It was
Speaker 1: edited by Lydia jene Kott and engineered by Sarah Bruguer.
Speaker 1: You can email us at problem at Pushkin dot FM.
Speaker 1: I'm Jacob Goldstein and we'll be back next week with
Speaker 1: another episode of What's Your Problem That's True sn