AI transcript
0:00:02 (upbeat music)
0:00:07 Pushkin.
0:00:14 When the war in Ukraine broke out a few years ago,
0:00:17 Laura Nickleson started hearing from Ukrainian doctors
0:00:20 who were treating soldiers at frontline hospitals.
0:00:23 – When patients would present to the hospital,
0:00:27 in many cases, these were soldiers
0:00:28 who had been injured in the war,
0:00:32 typically with blast injuries and shrapnel injuries,
0:00:36 because IED explosions are really one of the,
0:00:37 that’s modern warfare.
0:00:41 People lose limbs, and one of the reasons they lose limbs
0:00:44 is because the blood flow gets damaged and cut off,
0:00:47 and it’s very hard to restore that blood flow,
0:00:50 especially since the wounds are very contaminated.
0:00:55 These limbs are filled with shrapnel and metal and soil,
0:00:59 and it’s just, it’s very horrific in some cases.
0:01:01 – The doctors were getting in touch with Laura,
0:01:05 because she and her colleagues had spent more than 20 years
0:01:07 figuring out how to use human cells
0:01:11 to create new blood vessels outside the human body.
0:01:14 The idea is to create a supply of vessels
0:01:18 that surgeons can have on hand to implant into patients.
0:01:23 She calls these vessels HAVs, or human acellular vessels.
0:01:27 The HAVs have not yet been approved by the FDA,
0:01:30 but the Ukrainian surgeons thought they would be helpful.
0:01:32 So after getting approval from the Ukrainian Ministry
0:01:36 of Health, Laura and her colleagues sent HAVs
0:01:38 to several frontline hospitals in Ukraine.
0:01:43 – So when these patients would present to the hospital,
0:01:47 if the surgeon felt that the best treatment
0:01:49 for that patient was using the engineered vessel
0:01:53 to rapidly restore blood flow, he would do that.
0:01:57 And so that means cleaning out the wound,
0:01:59 the patient’s asleep at this time,
0:02:02 and they’re having their other injuries fixed as well.
0:02:06 But cleaning out the wound, isolating the damaged artery,
0:02:08 and then replacing the damaged segment
0:02:10 with our engineered vessel.
0:02:11 – And how did it go?
0:02:16 – Well, the outcomes in Ukraine went very well.
0:02:19 We treated a total of 19 patients
0:02:21 over a year-long humanitarian effort.
0:02:25 And in fact, we’re still following those patients now.
0:02:27 But what we found is that in the first month,
0:02:30 which is really the most important time
0:02:31 after somebody gets injured,
0:02:34 it’s how things go in the first month.
0:02:37 What we found in the first month is that
0:02:39 of the 19 patients we treated,
0:02:41 every single limb was salvaged.
0:02:46 There was no loss of limb, there was no loss of life.
0:02:49 And this is true even though some of the patients
0:02:51 we treated were very badly injured.
0:02:54 And in fact, one of the patients, the surgeon told us later
0:02:56 that he was quite sure this man would die.
0:03:00 But he survived and he walked out of the hospital
0:03:01 on his own leg.
0:03:06 So I believe in my heart that there are soldiers
0:03:09 in Ukraine who are walking and breathing now
0:03:12 who would not be if it weren’t for the HAV.
0:03:14 (upbeat music)
0:03:20 – I’m Jacob Goldstein and this is What’s Your Problem,
0:03:21 the show where I talk to people
0:03:24 who are trying to make technological progress.
0:03:27 My guest today is Laura Nicklison.
0:03:30 She’s the co-founder and CEO of Humasite.
0:03:32 Laura’s problem is this.
0:03:35 Can you use human cells to create a blood vessel
0:03:38 that is better, at least for some patients,
0:03:41 than any other options available today?
0:03:44 Laura has both a PhD and an MD.
0:03:47 She’s worked as a physician in the intensive care unit.
0:03:50 So to start, I asked her how she got
0:03:53 into the blood vessel business in the first place.
0:03:56 – Well, you know, I started working
0:04:01 trying to grow arteries from scratch in the mid 1990s.
0:04:06 I was training for my residency at Mass General Hospital.
0:04:09 I was taking care of patients in the operating room.
0:04:11 I was an anesthesiologist
0:04:13 and an intensive care unit doctor.
0:04:15 And I took care of a lot of patients
0:04:17 who had vascular disease in their heart
0:04:20 or their legs or elsewhere.
0:04:25 And diseases of arteries are still the biggest killers
0:04:27 of people in the Western world.
0:04:30 More so than cancer, more so than anything else.
0:04:32 – Well, sometimes we call it heart disease, right?
0:04:34 But it’s cardiovascular disease.
0:04:37 And the vascular piece there is vessels, right?
0:04:38 – Yes.
0:04:41 So it can be any artery supplying any part of your body.
0:04:46 And when those fail or clot or dilate or become infected,
0:04:50 they need to be bypassed or replaced.
0:04:54 And it’s a universal thing in all of healthcare.
0:04:58 And what I learned during my training
0:05:01 is that typically when we need to repair
0:05:05 or replace an artery, we rob Peter to pay Paul.
0:05:09 In other words, we cut open one part of your body
0:05:11 and take a vein out or an artery out.
0:05:14 And then we move it over and use that vein or artery
0:05:17 to repair the artery that’s broken.
0:05:20 – Like the classic is somebody’s getting a bypass surgery
0:05:22 for the blood vessels around their heart.
0:05:24 And the surgeon takes vessels from their leg, right?
0:05:26 You take vessels from the thigh
0:05:28 and you put it next to the heart.
0:05:29 – Yes, yes.
0:05:34 And as you might imagine, that always injures the patient
0:05:36 in the process of trying to fix the patient.
0:05:40 But importantly, not everybody has veins and arteries
0:05:43 hanging around in their body that are spare,
0:05:46 that are the right quality and the right size and shape
0:05:48 to fix the problem at hand.
0:05:51 And when that happens, surgeons are forced
0:05:55 to use plastic tubes, tubes made out of Teflon, for example.
0:05:59 And as you might imagine, if you sew a Teflon tube
0:06:03 into your vascular system, that often doesn’t work very well.
0:06:06 It clots, it gets infected, it can be problematic.
0:06:10 So I became really interested during my training
0:06:15 30 years ago in whether or not we could make new arteries
0:06:18 for patients that would behave like their own veins
0:06:22 and arteries, but whether we could manufacture them,
0:06:25 make basically spare parts that would be available
0:06:26 off the shelf.
0:06:30 – How was that idea received at that time?
0:06:37 – So people viewed it as very much like science fiction,
0:06:41 but also maybe not in a good way.
0:06:46 So some of my, some of even my close friends
0:06:49 when I started working on this, they kind of stepped back
0:06:53 and looked at me funny like, are you really serious here?
0:06:55 Is this something you’re really gonna try to do?
0:06:57 You know, grow an artery in a jar.
0:06:59 You know, nobody will take you seriously
0:07:00 if you try to do that.
0:07:04 So yes, that was absolutely the vibe in the 1990s.
0:07:08 – So you’re a medical resident, you’re a physician,
0:07:09 learning, you know, the clinical skills you need
0:07:11 to be a practicing physician, then you get this idea,
0:07:14 you wanna grow blood vessels in a jar.
0:07:18 How do you even do that?
0:07:21 Like they’re not doing that at Mass General.
0:07:26 – Yeah, so the idea of wanting to grow a vessel in a jar,
0:07:29 you’re right, it’s not an obvious idea
0:07:30 that pops into somebody’s head,
0:07:35 but I was fortunate enough to be able to work
0:07:36 in the laboratory of Robert Langer,
0:07:39 who’s still a very accomplished investigator,
0:07:43 one of the most famous investigators at MIT.
0:07:46 And as you may know, MIT is right across the river
0:07:49 from Mass General, where I was doing my residency.
0:07:52 And Langer’s lab was really one of the pioneers
0:07:56 in developing this whole concept of tissue engineering,
0:07:59 basically growing tissues from scratch.
0:08:03 So I developed this sort of hybrid identity
0:08:07 where I would do my clinical training during the day
0:08:10 at Mass General, and then after I was done with my cases,
0:08:13 I’d take the subway and go across the river
0:08:16 and then work in Langer’s lab in the afternoon and evening
0:08:19 and try to figure out how you grow an artery in a jar.
0:08:21 So I got very excited about this
0:08:25 and joined his lab in ’95
0:08:28 and worked for about three and a half years
0:08:32 and then was able to demonstrate and publish
0:08:35 really the first functional engineered artery
0:08:37 in a large animal.
0:08:40 We published that in 1999,
0:08:43 where I took cells from pigs
0:08:45 and grew arteries for those pigs
0:08:48 and then implanted them back and they worked.
0:08:50 And we published that in science
0:08:53 and at the time that made quite a splash.
0:08:57 So what was the state of tissue engineering
0:08:58 more generally at that time?
0:09:01 What could people do at that time?
0:09:06 – Well, the state of tissue engineering in the 1990s
0:09:10 was really, there had been some successes
0:09:14 in what I would call sort of simpler connective tissues.
0:09:17 So just to step back a little bit,
0:09:20 our bodies are divided into connective tissues
0:09:23 and non connective or organ tissues.
0:09:25 And connective tissues are any tissues
0:09:27 that hook one part of the body to the other.
0:09:32 So that’s skin, bone, blood vessel, tendon, what have you.
0:09:37 And then organs are obviously heart, liver, kidney,
0:09:38 stuff like that.
0:09:42 So there had been some successes even in the 1990s
0:09:47 in growing engineered tissues, for example, skin and cartilage.
0:09:49 And in fact, engineered skin and cartilage
0:09:53 by the mid to late 1990s were already on the market.
0:09:55 They were being used in patients.
0:10:00 And so the early feasibility
0:10:02 with some simpler connective tissues
0:10:05 had really already been demonstrated by that time.
0:10:09 – So, okay, this is whatever, 25-ish years ago.
0:10:13 Just at the end of last year, at the end of 2023,
0:10:16 you applied for FDA approval.
0:10:19 You’re likely to hear back in the next few months.
0:10:22 So what were a few of the things you had to figure out
0:10:25 to get from where you were 25 years ago
0:10:26 to where you are now?
0:10:28 – So it has been a long journey.
0:10:29 Initially, we thought, oh, well,
0:10:34 we’ll take a small biopsy from a patient who needs an artery
0:10:35 and we’ll grow their cells
0:10:37 and then we’ll make that patient a new artery
0:10:38 and then give it back to them.
0:10:40 – So it’s custom, it’s bespoke.
0:10:43 – It was bespoke tissue engineering.
0:10:46 The problem with that though is twofold.
0:10:48 One, it takes a long time.
0:10:49 – Yes.
0:10:51 – So if you’re a patient with chest pain.
0:10:54 – Yeah, or who just got blown up by an IED.
0:10:57 – Or who just got blown up by an IED,
0:10:58 you don’t really have three or four months
0:11:00 to wait around for a new artery.
0:11:03 So that’s fundamentally a problem.
0:11:05 But also what we found,
0:11:08 and this was during some work that I did
0:11:11 while I was still in academia at Duke University,
0:11:14 what we found is that for older patients
0:11:16 who have vascular disease,
0:11:19 if we try to take those cells from those patients
0:11:22 and grow new arteries for those patients,
0:11:23 it actually doesn’t work very well.
0:11:27 Their vessels are old and their cells are old.
0:11:31 And we found that and published that
0:11:34 and we have a whole series of papers on that.
0:11:37 But that really led us to a fundamental pivot
0:11:40 which was the insight that we could use
0:11:43 young healthy cells from humans,
0:11:46 use those to grow arteries.
0:11:49 But then after we grew the arteries from scratch,
0:11:54 we would wash the cells out of the engineered tissue.
0:11:58 And what that leaves behind is extracellular matrix,
0:12:00 which can then be implanted into anybody.
0:12:02 – I mean, that’s essentially where you arrived
0:12:04 and what you are doing now, right?
0:12:08 And so I wanna talk about that in a little more detail.
0:12:10 Basically, how it works.
0:12:13 How you make the thing that you make.
0:12:15 So where do you start?
0:12:18 – So we start with human cells
0:12:21 and the cells that we use.
0:12:25 So right now, human site has banks of human cells.
0:12:27 And in fact, we have enough cells banked
0:12:31 to support tissue production for the next 30 or 40 years.
0:12:32 We’ve got a lot of cells.
0:12:35 But where those cells come from
0:12:39 is actually they come from organ and tissue donors.
0:12:43 So if a patient dies and they become an organ donor,
0:12:44 their heart might go somewhere
0:12:47 and their liver might go somewhere else.
0:12:50 But there’s actually no transplantation use
0:12:52 for their blood vessels.
0:12:56 So we worked with organ procurement organizations
0:12:59 and we obtained consent from donor families.
0:13:03 And we obtained large blood vessels, aorta’s,
0:13:06 from hundreds of different organ donors.
0:13:08 We isolated cells from those donors
0:13:12 and then we did a tremendous amount of screening
0:13:15 to identify which cells would really be optimal
0:13:17 for growing new arteries.
0:13:19 And then we established banks.
0:13:23 So actually we have banks of donor cells now
0:13:25 that are derived from organ donors.
0:13:28 – So it’s like vials of cells in fluid
0:13:31 in the refrigerator or something like that?
0:13:34 – It’s vials of cells stored in liquid nitrogen.
0:13:36 So they’re extremely cold.
0:13:39 But that means that the cells can store for decades.
0:13:42 Okay, so very good.
0:13:47 That’s step one, get a lot of nice, healthy aorta cells.
0:13:51 And just to be clear, by the way,
0:13:55 are blood vessel cells the same in all of the vessels?
0:13:57 Dumb question, but are the cells of the aorta the same
0:14:00 as the cells in whatever other blood vessel?
0:14:03 – The cells, even within your aorta,
0:14:05 there’s different flavors of cells.
0:14:08 And the cells differ between arteries and veins
0:14:11 and big arteries and small arteries and capillaries.
0:14:14 So that was really part of the challenge for us,
0:14:17 was really identifying which subset
0:14:21 of cells in the aortas was really the most productive
0:14:25 for growing new arteries.
0:14:28 As it turns out, some of the cells in your body,
0:14:30 even if you’re an older person,
0:14:34 still have this sort of progenitor or stem-like capability.
0:14:38 And those cells we found could grow extensively
0:14:42 in our process and could grow large numbers of new arteries.
0:14:46 – Great, so you got not only a lot of cells,
0:14:48 you got a lot of the right kind of cells.
0:14:50 What do you do with them?
0:14:52 – Well, when we want to grow a batch of arteries,
0:14:56 right now we grow 200 arteries at a time
0:14:59 in a highly automated system that we’ve designed
0:15:02 and built over many years.
0:15:03 – Artery factory.
0:15:06 – It’s an artery factory, yes, yes.
0:15:10 In fact, we have eight installed units now.
0:15:13 Each unit, which we call a Luna 200 unit,
0:15:15 can grow 200 vessels at a time.
0:15:17 – And a unit is like a machine?
0:15:18 – It’s a machine, it’s a machine.
0:15:20 It’s about as big as a school bus.
0:15:21 – Okay.
0:15:24 – And it’s essentially a large incubator
0:15:28 where we control temperature and humidity and oxygen.
0:15:31 But we also have inside the school bus,
0:15:35 inside the incubator, we have bioreactor systems
0:15:39 where we can provide an environment
0:15:41 for the cells while they’re growing
0:15:46 so that the cells form new arteries.
0:15:48 But I’m sort of jumping ahead a little bit.
0:15:50 So when we start a batch,
0:15:53 what we do is we take a tiny vial of cells,
0:15:55 it’s about a fifth of a teaspoon.
0:15:57 It’s a little tiny volume.
0:16:00 And we thaw out those cells and then we grow them.
0:16:05 And we let them expand about 2000 fold.
0:16:06 – Okay.
0:16:09 – And then we gather all those cells
0:16:12 and then we essentially walk over
0:16:16 to one of our production units, one of our Luna 200s.
0:16:21 And in the Luna 200 is 200, what we call bioreactor bags.
0:16:27 Each bag has a scaffold inside of it that’s sterile.
0:16:32 And that scaffold is six millimeters in diameter
0:16:33 and 40 centimeters long.
0:16:36 So that’s the size of the artery we grow.
0:16:39 – So it’s made of like plastic or something?
0:16:41 – It’s a degradable plastic.
0:16:44 It’s actually, it’s the same material
0:16:47 that’s used in degradable sutures.
0:16:50 So each fiber is about the width of a cell.
0:16:53 And there’s a lot of empty space in between the fibers.
0:16:57 But the shape of the scaffold,
0:17:01 we can shape it into this six millimeter diameter tube
0:17:03 that’s 40 centimeters long.
0:17:06 And what we do is we take the cells that we grew
0:17:08 and we inject them into the bag.
0:17:13 And the cells stick onto the fibers of the scaffold.
0:17:16 It’s like a person hanging onto a metal pole
0:17:19 on building scaffolding.
0:17:21 If you think of it, that’s kind of what it’s like.
0:17:23 – And so the cells are grabbing sort of all over
0:17:26 this little plastic tube all over the scaffold.
0:17:30 – Yes, each cell grabs onto a metal pole
0:17:32 and they hang on for dear life.
0:17:37 And then we basically fill the bag,
0:17:39 the bioreactor bag with culture medium.
0:17:42 And then that culture medium is super secret.
0:17:44 It has lots of yummy stuff in it
0:17:47 that convinces the cells to grow.
0:17:50 And while they’re growing, they secrete proteins
0:17:54 like collagen and other matrix molecules.
0:17:57 What also happens while the cells are growing
0:18:01 in the culture medium is we’ve designed the bioreactor bag
0:18:03 so that we can stretch the cells
0:18:07 as if the cells are in the wall of an artery
0:18:09 and they’re feeling your heartbeat.
0:18:13 – Ah-ha, because arteries need to get wider
0:18:16 and get narrower as the pulse of blood comes in and out.
0:18:17 – Yes, yes.
0:18:17 So if you put your–
0:18:18 – It’s like why there’s two different numbers
0:18:20 in your blood pressure reading.
0:18:23 – Exactly, there’s a higher pressure and a lower pressure.
0:18:25 And if you put your finger on your wrist,
0:18:27 you can feel your pulse.
0:18:29 That pulse is your artery distanding
0:18:33 and then recoiling every time your heart beats.
0:18:35 Well, it turns out we learned very early.
0:18:38 We figured out when I was working in Langer’s lab
0:18:41 in the ’90s that if we didn’t stretch these cells
0:18:44 while they were growing, they didn’t really make an artery
0:18:46 ’cause they didn’t know they were supposed to do that.
0:18:48 – So they would be too rigid.
0:18:49 They wouldn’t be able to–
0:18:52 – They would be disorganized, actually.
0:18:54 They would just grow randomly
0:18:56 ’cause they didn’t know what they were supposed to be doing.
0:19:01 – So it’s like that pulse kind of tells them
0:19:03 how to grow and organize themselves.
0:19:04 – Yes, absolutely.
0:19:05 – Ah, it’s really interesting.
0:19:06 – It’s really interesting, yeah.
0:19:09 – So how do you, so you do that in the bag?
0:19:10 How do you get them to–
0:19:11 – Yes.
0:19:13 – So you have a little sort of imitation heartbeat
0:19:14 sort of in the bag?
0:19:18 – We have a little imitation heartbeat in the bag, yes.
0:19:21 And every vessel gets stretched the same amount
0:19:24 and they get stretched cyclically by this heartbeat
0:19:26 for the entire two-month culture duration.
0:19:30 – So they spend two months growing
0:19:34 and learning how to be cells in an artery
0:19:39 and filling in all the spaces on the scaffold,
0:19:41 on the little plastic tube.
0:19:43 What happens at the end of that two months?
0:19:44 – Well, at the end of the two months,
0:19:45 a couple things have happened.
0:19:50 One is that scaffolding, which I said is degradable,
0:19:54 has mostly degraded, so it’s pretty much all gone.
0:19:58 So what we have by that time is a human artery
0:20:03 that has these cells and also the collagen matrix proteins
0:20:06 that they made, and there’s really no scaffold left.
0:20:12 So in a final step, we drain out the culture medium
0:20:15 that we use to convince the cells to grow
0:20:19 and then we replace it with detergents.
0:20:23 And we basically, we spend five days
0:20:26 and we wash the cells out of the artery.
0:20:29 – Huh, so after two months when you take it out,
0:20:33 it feels like it’s a lot like an artery in my body,
0:20:35 in your body, in anybody’s body.
0:20:39 But that’s not good because if you put that in a patient,
0:20:42 you’ll have a bad immune response.
0:20:45 That’s presumably the problem, why you can’t just use that.
0:20:46 – That’s the reason, yes.
0:20:49 Because again, these are cells from a cell bank.
0:20:52 So if I grow that artery and then I implant it in you,
0:20:54 your body will reject it.
0:20:55 ‘Cause it’s a transplant. – It’s a transplant.
0:20:57 And suddenly I’m getting a transplant.
0:21:02 And so what is that final step or that next step?
0:21:06 – So the final step, we call that decellularization.
0:21:09 So we rinse away the cells,
0:21:13 which are really the part that creates the immune rejection.
0:21:16 But what we leave behind and what we’re very careful
0:21:20 not to disturb is the extracellular matrix proteins,
0:21:22 like the collagen that I mentioned.
0:21:25 There’s actually 40 or 50 proteins there.
0:21:28 The reason that’s important is because it’s really
0:21:32 the collagen and the proteins that give the vessel
0:21:35 all of its mechanical properties.
0:21:38 So actually washing the cells out of the tissue
0:21:40 doesn’t change how strong it is.
0:21:43 It’s still just as strong as your arteries
0:21:45 after we wash the cells out.
0:21:48 The cells are really there to be little protein factories.
0:21:49 – Yeah, right.
0:21:51 – But they themselves are not very strong.
0:21:56 But because collagen is so important,
0:21:59 like for example, your collagen and my collagen
0:22:01 are identical.
0:22:02 They’re identical.
0:22:03 – You’re saying there’s no kind of,
0:22:06 there’s no potential immune response.
0:22:07 It’s just protein.
0:22:09 It’s just these exact same protein.
0:22:10 You couldn’t tell the difference.
0:22:12 You couldn’t tell who it came from.
0:22:14 – Yes, your body can’t tell the difference.
0:22:18 And so we’ve implanted these decelularized,
0:22:22 engineered arteries into nearly 600 patients
0:22:23 over the last 11 years.
0:22:26 We’ve never seen a single episode of rejection.
0:22:30 – Because in an immune sense, there’s nothing to reject.
0:22:32 – That’s what we believe, yes.
0:22:36 – So now it’s like kind of like a dead artery,
0:22:40 an artery without any personality, a generic artery.
0:22:47 You put it in a person, in a patient, what happens then?
0:22:49 – Well, there’s a couple of things that happen.
0:22:51 The first thing that happens is that the artery
0:22:52 works as it should.
0:22:57 So the main job of arteries is to conduct blood flow
0:22:59 so that you can get blood from point A to point B.
0:23:02 So that happens as soon as the surgeon sows it in
0:23:04 and takes the clamps off.
0:23:07 So some people worry, gee, we wash the cells out,
0:23:09 will it be leaky?
0:23:11 That doesn’t happen.
0:23:12 We don’t see that.
0:23:18 But what’s probably cooler is that over time,
0:23:23 cells from the patient see this naked artery
0:23:25 and to them, it sort of looks like
0:23:27 an empty apartment building.
0:23:31 And what we’ve seen happen, in fact, we’ve published this,
0:23:36 is that cells from the patient migrate into the
0:23:42 acellular artery and they start off being progenitor cells,
0:23:44 but they become vascular cells.
0:23:49 So over a period of months, this non-living thing becomes
0:23:52 a living artery and it’s the patient’s own.
0:23:55 So this is really, I think,
0:23:58 this is regenerative medicine in the truest sense.
0:24:03 – So can you tell the difference, whatever,
0:24:05 a year later between the section of artery
0:24:08 that you put in and the patient’s own artery?
0:24:10 – You can tell differences.
0:24:12 There are still subtle differences.
0:24:16 There is one stretchy protein called elastin,
0:24:18 which is in all of our arteries,
0:24:21 but the engineered arteries don’t have elastin,
0:24:24 so that’s actually the easiest way to tell.
0:24:28 Aside from that, there’s not a lot of differences.
0:24:32 – Does the absence of elastin make a functional difference?
0:24:34 – It doesn’t seem to.
0:24:37 – This is something that I used to worry about
0:24:40 as a younger professor 10, 15, 20 years ago,
0:24:44 but over 1,000 patient years of exposure
0:24:46 tells us that it probably doesn’t matter.
0:24:50 – It’s weird that there’s a thing in our arteries
0:24:51 that we could do without.
0:24:53 You’d think that would, you know,
0:24:56 the way fish that live in caves for a million years
0:24:59 don’t have eyes anymore because it’s costly to have eyes
0:25:01 and if you don’t need them, they evolve away.
0:25:03 – Well, I think that’s the difference
0:25:06 between having no elastin in your body,
0:25:10 but having or not having elastin just in a short segment.
0:25:13 So if you have no elastin in your whole body,
0:25:17 that makes life very, very hard for your heart.
0:25:19 However, if it’s just a short segment
0:25:22 of the vessels in your body that don’t have elastin,
0:25:24 your heart doesn’t care too much.
0:25:27 (upbeat music)
0:25:28 – We’ll be back in a minute.
0:25:31 (upbeat music)
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0:26:25 – Laura’s company, Humasite,
0:26:28 applied late last year for FDA approval.
0:26:29 They expect to hear back this summer.
0:26:32 And she told me about the evidence
0:26:34 that made her think, that made the company think,
0:26:38 that they were finally ready to apply for FDA approval
0:26:42 for widespread use of these vessels they’re creating.
0:26:46 – So the trial that is supporting our current application
0:26:50 at the FDA was conducted at 19 trauma centers
0:26:52 in the U.S. and Israel.
0:26:55 And we treated a total of 70 patients
0:26:59 who had all sorts of injuries.
0:27:01 You know, car accidents, gunshot wounds,
0:27:03 industrial accidents.
0:27:05 We treated a guy who worked on a farm
0:27:07 who was crushed by a cow.
0:27:10 We treated a woman who was crushed by a crane on a dock.
0:27:14 I mean, we just all sorts of terrible injuries.
0:27:16 And then we followed those patients.
0:27:18 Many of them were still following.
0:27:21 But it was really the data from that pivotal trial
0:27:26 that showed really excellent outcomes in terms of safety
0:27:30 but also in terms of how well blood flow was restored
0:27:34 and a very low number of amputations and infections.
0:27:38 So seeing all of that clinical data together
0:27:40 from this pivotal trial
0:27:42 and then combined with the Ukraine experience
0:27:45 because the Ukraine humanitarian effort
0:27:48 was ongoing at the same time we were doing this pivotal trial.
0:27:51 So putting all of that information together
0:27:53 is what really formed the basis
0:27:56 of our filing with the FDA last year.
0:28:00 – You mentioned that there are other options.
0:28:04 Where do your arteries fit in the sort of,
0:28:06 you know, comparative landscape?
0:28:08 Like when is something else better
0:28:10 and when is one of your arteries better?
0:28:12 – Well, this is something that, you know,
0:28:16 the FDA would argue is probably their decision to make.
0:28:18 Our argument is that in patients
0:28:22 who don’t have their own vein available
0:28:23 and for injured patients,
0:28:26 it may be because their limbs are injured.
0:28:30 It may be because the need to restore blood flow
0:28:34 is so acute that the surgeons don’t have that extra hour
0:28:35 to harvest the vein.
0:28:37 It could be that the surgeon doesn’t wanna
0:28:39 injure the patient further.
0:28:42 So in patients in whom vein is not feasible,
0:28:48 our argument is that the HAV is an excellent option.
0:28:53 And our data showed when we compared our outcomes
0:28:58 to outcomes of patients who are treated with plastic graphs,
0:29:02 like made out of Teflon, in trauma,
0:29:04 our data showed that our outcomes
0:29:08 are substantially better than plastic graphs.
0:29:11 – What are some of the next things that you’re working on?
0:29:14 Like what are you trying to figure out now?
0:29:16 – Well, on the clinical side,
0:29:19 we have trials that are under ways
0:29:21 that we’re still collecting data on
0:29:23 in patients with kidney failure,
0:29:26 who were studying our engineered vessels
0:29:32 as what we call a dialysis access,
0:29:35 which is where our vessels are sewn into the patient’s arm
0:29:37 between an artery and a vein.
0:29:41 And then that vessel is used in the dialysis clinic
0:29:44 where nurses poke needles into the vessel
0:29:47 and use that so the patient can get dialysis.
0:29:50 So we’re studying that indication.
0:29:53 And in fact, we have another pivotal trial
0:29:56 that we expect to read out in the third quarter of this year
0:30:01 in 2024 that will tell us if the HAV works better
0:30:07 in dialysis than basically the gold standard,
0:30:09 which is where a surgeon sews an artery
0:30:11 and a vein together directly.
0:30:13 – So that’s the kind of short-term future
0:30:18 it’s basically trying to get the dialysis-related indication.
0:30:21 When you think more long-term,
0:30:24 if you think, I don’t even know how many years that is for you.
0:30:26 Is it five years? Is it 10 years?
0:30:28 Like what do you think about?
0:30:29 – So for the last several years,
0:30:32 we’ve been making smaller diameter vessels
0:30:35 that are the right size for heart bypass.
0:30:39 And we’ve actually been testing
0:30:41 these three and a half millimeter vessels
0:30:45 doing heart bypasses in primates,
0:30:48 non-human primates and other large animals.
0:30:51 And we’re collecting long-term data
0:30:56 to submit as a file to the FDA in order to gain approval
0:30:59 to do a phase one trial in patients who need a heart bypass
0:31:04 but who don’t have their own vein to do the bypass.
0:31:08 So we would hope to start that first in human trial
0:31:11 in heart bypass in the next couple of years.
0:31:13 So bypass is a, you know,
0:31:17 unfortunately wildly common procedure.
0:31:20 My dad had one, my grandfather had a few.
0:31:23 I’m taking statins and running all the time
0:31:25 in hopes that I’ll dodge that bullet, but who knows?
0:31:29 So presumably that would be a very large market.
0:31:33 I mean, it’s also the case that many patients
0:31:35 are able to use their own veins.
0:31:37 You mentioned, you’re thinking about patients who can’t.
0:31:40 In what instances are graphs unavailable
0:31:41 for patients getting bypass?
0:31:43 And what do doctors do now in those instances?
0:31:46 – Well, there’s lots of situations
0:31:50 where patients who need a vein for heart bypass don’t have it.
0:31:52 So for example, if you have varicose veins,
0:31:56 if your veins are very dilated, surgeons can’t use them.
0:32:01 In the modern era, vein clinics are
0:32:03 sclerosing people’s veins all the time.
0:32:08 So that ladies can have beautiful legs at the beach,
0:32:10 which is great in the short term,
0:32:11 but not so good in the long term.
0:32:14 And then lastly, as we know,
0:32:18 there’s a growing obesity and diabetes epidemic
0:32:21 in the United States, most of the Western world.
0:32:23 For those patients, if you cut into their legs
0:32:25 and take their vein out,
0:32:27 they have a higher rate of complications.
0:32:31 Their incisions don’t heal, they get infected.
0:32:32 They have all sorts of problems.
0:32:35 – Are there not Teflon artificial veins
0:32:37 that can be used for bypass?
0:32:40 – There’s nothing artificial
0:32:44 that works for those smaller diameter vessels in your heart.
0:32:50 Despite a huge need, there simply isn’t anything.
0:32:53 – So you said that when you started out 25, 30 years ago,
0:32:56 making a connective tissue like blood vessels,
0:32:57 like what you’re doing,
0:33:00 seemed much easier than making solid organs.
0:33:02 And so I’m curious after all this time
0:33:04 and all the advancements there have been,
0:33:07 does making a solid organ in a lab
0:33:09 still feel wild hard?
0:33:13 – It’s still wild hard,
0:33:16 but it’s starting to feel tractable.
0:33:19 So one of the parts that we haven’t talked about is,
0:33:22 I’ve had this dual life for many years as a,
0:33:24 right now I’m the CEO of Humasite
0:33:26 and I’m not an academic anymore,
0:33:30 but for many years I sort of had one foot in academia
0:33:32 and one foot in my company.
0:33:36 And while I was working as a professor at Yale,
0:33:39 we were the first lab to actually be able
0:33:44 to grow engineered lungs and implant them in rats
0:33:47 and showed that they could exchange gas for a few hours.
0:33:52 So we have a pathway, I believe,
0:33:56 to growing more complex tissues, lungs in particular.
0:34:00 And in fact, some of my former trainees from my lab
0:34:03 are off-scattered at different institutions
0:34:05 working on that problem right now.
0:34:08 – On lab-grown lungs in particular?
0:34:09 – Lab-grown lungs, yes.
0:34:13 – Are lungs less complex than other organs?
0:34:15 Is that why lungs?
0:34:19 – Lungs are not less complex,
0:34:21 but lungs, interestingly,
0:34:23 they’re the only organ in your body
0:34:26 that’s mostly empty space.
0:34:29 And in biology, in biotechnology,
0:34:32 we’re very good at growing thin layers of cells
0:34:36 or monolayers or thin collections of cells.
0:34:38 One of the things that we did figure out
0:34:41 in my academic lab is that
0:34:45 instead of using a plastic scaffold for lungs,
0:34:50 what we can probably do is take a native lung,
0:34:55 either a human lung or maybe a primate lung or a pig lung,
0:35:00 and decelularize that lung and use that as a scaffold.
0:35:03 In that case, we could maybe take stem cells
0:35:07 from the patient and repopulate that scaffold
0:35:09 that has all of the structure of the lung,
0:35:11 all the air sacs, all the blood vessels,
0:35:14 all of that important lung structure.
0:35:17 If we can repopulate that with cells,
0:35:20 then we’re basically, we kind of have a leg up,
0:35:22 we’ve got the lung structure to start with,
0:35:25 and then we just repopulate it with cells from the patient,
0:35:28 and then we’ve got a designer organ.
0:35:32 (upbeat music)
0:35:34 We’ll be back in a minute with the lightning round.
0:35:47 So I’m cognizant of the time.
0:35:52 I just wanna ask you some lightning round questions
0:35:53 to finish.
0:35:57 They will be slightly more random
0:35:59 than the questions I’ve asked you so far.
0:36:04 What’s one thing you learned from Bob Langer?
0:36:08 – I learned from Bob Langer
0:36:11 that time is the one thing you can’t get back,
0:36:18 that getting things done cost effort
0:36:20 and they cost money and they cost time.
0:36:25 You can get more effort and you can get more money,
0:36:26 but you can’t get more time.
0:36:31 So he was always focused on finding the most efficient way
0:36:35 to get something done that took the least amount of time
0:36:38 because as it turns out, everything takes longer
0:36:39 than you think it’s gonna.
0:36:44 – It’s interesting to think about him that way, right?
0:36:45 ‘Cause I interviewed him and I was like,
0:36:48 how did you do so many things?
0:36:50 And he, I don’t know if he knew,
0:36:52 but like that answer that you just gave
0:36:55 is a pretty good answer for how he did so many things.
0:37:00 So it was what the mid 90s is that right?
0:37:05 When you started sort of getting into regenerative medicine.
0:37:09 And I’m curious, you know, that’s 30 years ago now.
0:37:14 And I’m curious, looking back now,
0:37:17 it’s sort of what you thought then,
0:37:18 what is something that’s progressed
0:37:21 more quickly than you thought it would?
0:37:23 – Tools.
0:37:26 Tools.
0:37:30 One of the reasons that cell therapy
0:37:32 and regenerative medicine is taking off now
0:37:35 and will continue to just explode
0:37:38 in the next couple of decades is tools.
0:37:41 We can look at a tissue that we’re growing
0:37:47 and sort of generate sort of a report card of,
0:37:51 here’s how the cells are behaving,
0:37:53 you know, 15% of the cells are behaving correctly,
0:37:57 85% of the cells are not doing what they’re supposed to do.
0:37:59 And I can compare that report card
0:38:00 to what a native tissue looks like.
0:38:03 And then I can go back and fix what I’m doing
0:38:06 on the engineered side and just iterate that way.
0:38:07 It allows you to make a roadmap.
0:38:10 – What’s something that has progressed more slowly
0:38:11 than you would have thought?
0:38:18 – I think that the development
0:38:22 of functional connective tissues
0:38:25 has progressed more slowly than I would have thought.
0:38:26 – The thing you do?
0:38:28 – The thing I do.
0:38:29 The thing I do.
0:38:32 And I’m surprised at that.
0:38:36 If we look, so as I said, in the 1990s,
0:38:40 there were approved versions of tissue engineered cartilage
0:38:42 and tissue engineered skin
0:38:44 that were on the market in the US or Europe.
0:38:46 – Did those just turn out to be way easier
0:38:48 than everything else or what?
0:38:50 – They are, they’re easier.
0:38:52 The tissues are simpler.
0:38:57 And what we would say are design requirements
0:38:59 are a little bit less stringent.
0:39:03 So what has progressed more slowly than I would have thought
0:39:06 is making tissues that have tougher design criteria
0:39:09 and doing that successfully.
0:39:12 – Seems like you’re almost there.
0:39:15 – We’re almost there.
0:39:17 But it does, I’ve been working on it for 30 years.
0:39:18 It does take time.
0:39:22 – Did you feel like you were almost there 10 years ago?
0:39:24 – I felt like I was almost there 20 years ago.
0:39:27 (laughing)
0:39:29 – But this time you mean it.
0:39:30 – This time I mean it.
0:39:35 But no, I think it’s to make tissues,
0:39:39 you have to understand the cell biology
0:39:42 and that single cell information that I mentioned.
0:39:44 But you also really have to come to grips
0:39:48 with what the tissue does and what characteristics
0:39:50 the whole tissue must have in order to function.
0:39:54 And that’s a complicated set of problems.
0:39:57 And it takes, one person can’t do it all.
0:39:59 It takes a really terrific team working on it
0:40:01 for a long time.
0:40:03 – Do you think that having a founding team
0:40:06 that was all women affected the culture of the company?
0:40:09 – It affected a lot of things.
0:40:11 It affected the culture of the company.
0:40:17 Humasite has never suffered from a sense
0:40:19 that women can’t be heard in a meeting.
0:40:24 It’s actually allowed us to attract and retain
0:40:26 incredibly smart and high powered women
0:40:28 because they know they will never have to fight
0:40:30 that uphill battle.
0:40:33 So it actually gives us an edge in terms of recruitment.
0:40:37 But in retrospect, now having been at this
0:40:41 for nearly 20 years, I would say that in the early years,
0:40:44 I think it made it harder for us to raise money.
0:40:49 People write about this and people used to ask me
0:40:52 about it early on and I sort of discarded it
0:40:54 as being paranoid.
0:40:58 But now looking back, I think it hurt us.
0:41:02 I just think that people, there’s an expectation that,
0:41:04 well, if this is an all women company,
0:41:07 then maybe this isn’t gonna work.
0:41:09 – What’s one thing you wish more people understood
0:41:10 about cells?
0:41:18 – I wish that people appreciated how smart cells are.
0:41:19 – What do you mean?
0:41:25 – Well, what I’ve learned is that if I work
0:41:30 with the right starting cells, if I give them
0:41:35 about eight cues, not one cue, but it’s not 1,000 cues.
0:41:38 If I give them about eight cues,
0:41:40 couple of the right growth factors,
0:41:44 right amount of stretch, right temperature,
0:41:48 right oxygen level, if I give them about eight cues,
0:41:50 they take it and run with it.
0:41:53 And without any supervision from me,
0:41:56 they make a brand new artery that looks and feels
0:41:57 like the real thing.
0:42:01 And that’s a remarkable amount of intelligence
0:42:03 inside a little tiny cell.
0:42:06 So our cells are very self-directed.
0:42:08 They’re very smart.
0:42:11 And in order to coax them to make spare parts,
0:42:14 we just have to figure out what that right handful
0:42:15 of cues is.
0:42:18 (upbeat music)
0:42:21 – Lauren Nicholson is the co-founder
0:42:22 and CEO of Humasite.
0:42:26 Today’s show was produced by Gabriel Hunter-Chang.
0:42:29 It was edited by Lydia Jean-Cott
0:42:31 and engineered by Sarah Brugger.
0:42:35 You can email us at problem@pushkin.fm.
0:42:37 I’m Jacob Goldstein and we’ll be back next week
0:42:39 with another episode of What’s Your Problem?
0:42:41 (upbeat music)
0:42:44 (upbeat music)
0:42:47 (upbeat music)
0:42:57 [BLANK_AUDIO]
0:00:07 Pushkin.
0:00:14 When the war in Ukraine broke out a few years ago,
0:00:17 Laura Nickleson started hearing from Ukrainian doctors
0:00:20 who were treating soldiers at frontline hospitals.
0:00:23 – When patients would present to the hospital,
0:00:27 in many cases, these were soldiers
0:00:28 who had been injured in the war,
0:00:32 typically with blast injuries and shrapnel injuries,
0:00:36 because IED explosions are really one of the,
0:00:37 that’s modern warfare.
0:00:41 People lose limbs, and one of the reasons they lose limbs
0:00:44 is because the blood flow gets damaged and cut off,
0:00:47 and it’s very hard to restore that blood flow,
0:00:50 especially since the wounds are very contaminated.
0:00:55 These limbs are filled with shrapnel and metal and soil,
0:00:59 and it’s just, it’s very horrific in some cases.
0:01:01 – The doctors were getting in touch with Laura,
0:01:05 because she and her colleagues had spent more than 20 years
0:01:07 figuring out how to use human cells
0:01:11 to create new blood vessels outside the human body.
0:01:14 The idea is to create a supply of vessels
0:01:18 that surgeons can have on hand to implant into patients.
0:01:23 She calls these vessels HAVs, or human acellular vessels.
0:01:27 The HAVs have not yet been approved by the FDA,
0:01:30 but the Ukrainian surgeons thought they would be helpful.
0:01:32 So after getting approval from the Ukrainian Ministry
0:01:36 of Health, Laura and her colleagues sent HAVs
0:01:38 to several frontline hospitals in Ukraine.
0:01:43 – So when these patients would present to the hospital,
0:01:47 if the surgeon felt that the best treatment
0:01:49 for that patient was using the engineered vessel
0:01:53 to rapidly restore blood flow, he would do that.
0:01:57 And so that means cleaning out the wound,
0:01:59 the patient’s asleep at this time,
0:02:02 and they’re having their other injuries fixed as well.
0:02:06 But cleaning out the wound, isolating the damaged artery,
0:02:08 and then replacing the damaged segment
0:02:10 with our engineered vessel.
0:02:11 – And how did it go?
0:02:16 – Well, the outcomes in Ukraine went very well.
0:02:19 We treated a total of 19 patients
0:02:21 over a year-long humanitarian effort.
0:02:25 And in fact, we’re still following those patients now.
0:02:27 But what we found is that in the first month,
0:02:30 which is really the most important time
0:02:31 after somebody gets injured,
0:02:34 it’s how things go in the first month.
0:02:37 What we found in the first month is that
0:02:39 of the 19 patients we treated,
0:02:41 every single limb was salvaged.
0:02:46 There was no loss of limb, there was no loss of life.
0:02:49 And this is true even though some of the patients
0:02:51 we treated were very badly injured.
0:02:54 And in fact, one of the patients, the surgeon told us later
0:02:56 that he was quite sure this man would die.
0:03:00 But he survived and he walked out of the hospital
0:03:01 on his own leg.
0:03:06 So I believe in my heart that there are soldiers
0:03:09 in Ukraine who are walking and breathing now
0:03:12 who would not be if it weren’t for the HAV.
0:03:14 (upbeat music)
0:03:20 – I’m Jacob Goldstein and this is What’s Your Problem,
0:03:21 the show where I talk to people
0:03:24 who are trying to make technological progress.
0:03:27 My guest today is Laura Nicklison.
0:03:30 She’s the co-founder and CEO of Humasite.
0:03:32 Laura’s problem is this.
0:03:35 Can you use human cells to create a blood vessel
0:03:38 that is better, at least for some patients,
0:03:41 than any other options available today?
0:03:44 Laura has both a PhD and an MD.
0:03:47 She’s worked as a physician in the intensive care unit.
0:03:50 So to start, I asked her how she got
0:03:53 into the blood vessel business in the first place.
0:03:56 – Well, you know, I started working
0:04:01 trying to grow arteries from scratch in the mid 1990s.
0:04:06 I was training for my residency at Mass General Hospital.
0:04:09 I was taking care of patients in the operating room.
0:04:11 I was an anesthesiologist
0:04:13 and an intensive care unit doctor.
0:04:15 And I took care of a lot of patients
0:04:17 who had vascular disease in their heart
0:04:20 or their legs or elsewhere.
0:04:25 And diseases of arteries are still the biggest killers
0:04:27 of people in the Western world.
0:04:30 More so than cancer, more so than anything else.
0:04:32 – Well, sometimes we call it heart disease, right?
0:04:34 But it’s cardiovascular disease.
0:04:37 And the vascular piece there is vessels, right?
0:04:38 – Yes.
0:04:41 So it can be any artery supplying any part of your body.
0:04:46 And when those fail or clot or dilate or become infected,
0:04:50 they need to be bypassed or replaced.
0:04:54 And it’s a universal thing in all of healthcare.
0:04:58 And what I learned during my training
0:05:01 is that typically when we need to repair
0:05:05 or replace an artery, we rob Peter to pay Paul.
0:05:09 In other words, we cut open one part of your body
0:05:11 and take a vein out or an artery out.
0:05:14 And then we move it over and use that vein or artery
0:05:17 to repair the artery that’s broken.
0:05:20 – Like the classic is somebody’s getting a bypass surgery
0:05:22 for the blood vessels around their heart.
0:05:24 And the surgeon takes vessels from their leg, right?
0:05:26 You take vessels from the thigh
0:05:28 and you put it next to the heart.
0:05:29 – Yes, yes.
0:05:34 And as you might imagine, that always injures the patient
0:05:36 in the process of trying to fix the patient.
0:05:40 But importantly, not everybody has veins and arteries
0:05:43 hanging around in their body that are spare,
0:05:46 that are the right quality and the right size and shape
0:05:48 to fix the problem at hand.
0:05:51 And when that happens, surgeons are forced
0:05:55 to use plastic tubes, tubes made out of Teflon, for example.
0:05:59 And as you might imagine, if you sew a Teflon tube
0:06:03 into your vascular system, that often doesn’t work very well.
0:06:06 It clots, it gets infected, it can be problematic.
0:06:10 So I became really interested during my training
0:06:15 30 years ago in whether or not we could make new arteries
0:06:18 for patients that would behave like their own veins
0:06:22 and arteries, but whether we could manufacture them,
0:06:25 make basically spare parts that would be available
0:06:26 off the shelf.
0:06:30 – How was that idea received at that time?
0:06:37 – So people viewed it as very much like science fiction,
0:06:41 but also maybe not in a good way.
0:06:46 So some of my, some of even my close friends
0:06:49 when I started working on this, they kind of stepped back
0:06:53 and looked at me funny like, are you really serious here?
0:06:55 Is this something you’re really gonna try to do?
0:06:57 You know, grow an artery in a jar.
0:06:59 You know, nobody will take you seriously
0:07:00 if you try to do that.
0:07:04 So yes, that was absolutely the vibe in the 1990s.
0:07:08 – So you’re a medical resident, you’re a physician,
0:07:09 learning, you know, the clinical skills you need
0:07:11 to be a practicing physician, then you get this idea,
0:07:14 you wanna grow blood vessels in a jar.
0:07:18 How do you even do that?
0:07:21 Like they’re not doing that at Mass General.
0:07:26 – Yeah, so the idea of wanting to grow a vessel in a jar,
0:07:29 you’re right, it’s not an obvious idea
0:07:30 that pops into somebody’s head,
0:07:35 but I was fortunate enough to be able to work
0:07:36 in the laboratory of Robert Langer,
0:07:39 who’s still a very accomplished investigator,
0:07:43 one of the most famous investigators at MIT.
0:07:46 And as you may know, MIT is right across the river
0:07:49 from Mass General, where I was doing my residency.
0:07:52 And Langer’s lab was really one of the pioneers
0:07:56 in developing this whole concept of tissue engineering,
0:07:59 basically growing tissues from scratch.
0:08:03 So I developed this sort of hybrid identity
0:08:07 where I would do my clinical training during the day
0:08:10 at Mass General, and then after I was done with my cases,
0:08:13 I’d take the subway and go across the river
0:08:16 and then work in Langer’s lab in the afternoon and evening
0:08:19 and try to figure out how you grow an artery in a jar.
0:08:21 So I got very excited about this
0:08:25 and joined his lab in ’95
0:08:28 and worked for about three and a half years
0:08:32 and then was able to demonstrate and publish
0:08:35 really the first functional engineered artery
0:08:37 in a large animal.
0:08:40 We published that in 1999,
0:08:43 where I took cells from pigs
0:08:45 and grew arteries for those pigs
0:08:48 and then implanted them back and they worked.
0:08:50 And we published that in science
0:08:53 and at the time that made quite a splash.
0:08:57 So what was the state of tissue engineering
0:08:58 more generally at that time?
0:09:01 What could people do at that time?
0:09:06 – Well, the state of tissue engineering in the 1990s
0:09:10 was really, there had been some successes
0:09:14 in what I would call sort of simpler connective tissues.
0:09:17 So just to step back a little bit,
0:09:20 our bodies are divided into connective tissues
0:09:23 and non connective or organ tissues.
0:09:25 And connective tissues are any tissues
0:09:27 that hook one part of the body to the other.
0:09:32 So that’s skin, bone, blood vessel, tendon, what have you.
0:09:37 And then organs are obviously heart, liver, kidney,
0:09:38 stuff like that.
0:09:42 So there had been some successes even in the 1990s
0:09:47 in growing engineered tissues, for example, skin and cartilage.
0:09:49 And in fact, engineered skin and cartilage
0:09:53 by the mid to late 1990s were already on the market.
0:09:55 They were being used in patients.
0:10:00 And so the early feasibility
0:10:02 with some simpler connective tissues
0:10:05 had really already been demonstrated by that time.
0:10:09 – So, okay, this is whatever, 25-ish years ago.
0:10:13 Just at the end of last year, at the end of 2023,
0:10:16 you applied for FDA approval.
0:10:19 You’re likely to hear back in the next few months.
0:10:22 So what were a few of the things you had to figure out
0:10:25 to get from where you were 25 years ago
0:10:26 to where you are now?
0:10:28 – So it has been a long journey.
0:10:29 Initially, we thought, oh, well,
0:10:34 we’ll take a small biopsy from a patient who needs an artery
0:10:35 and we’ll grow their cells
0:10:37 and then we’ll make that patient a new artery
0:10:38 and then give it back to them.
0:10:40 – So it’s custom, it’s bespoke.
0:10:43 – It was bespoke tissue engineering.
0:10:46 The problem with that though is twofold.
0:10:48 One, it takes a long time.
0:10:49 – Yes.
0:10:51 – So if you’re a patient with chest pain.
0:10:54 – Yeah, or who just got blown up by an IED.
0:10:57 – Or who just got blown up by an IED,
0:10:58 you don’t really have three or four months
0:11:00 to wait around for a new artery.
0:11:03 So that’s fundamentally a problem.
0:11:05 But also what we found,
0:11:08 and this was during some work that I did
0:11:11 while I was still in academia at Duke University,
0:11:14 what we found is that for older patients
0:11:16 who have vascular disease,
0:11:19 if we try to take those cells from those patients
0:11:22 and grow new arteries for those patients,
0:11:23 it actually doesn’t work very well.
0:11:27 Their vessels are old and their cells are old.
0:11:31 And we found that and published that
0:11:34 and we have a whole series of papers on that.
0:11:37 But that really led us to a fundamental pivot
0:11:40 which was the insight that we could use
0:11:43 young healthy cells from humans,
0:11:46 use those to grow arteries.
0:11:49 But then after we grew the arteries from scratch,
0:11:54 we would wash the cells out of the engineered tissue.
0:11:58 And what that leaves behind is extracellular matrix,
0:12:00 which can then be implanted into anybody.
0:12:02 – I mean, that’s essentially where you arrived
0:12:04 and what you are doing now, right?
0:12:08 And so I wanna talk about that in a little more detail.
0:12:10 Basically, how it works.
0:12:13 How you make the thing that you make.
0:12:15 So where do you start?
0:12:18 – So we start with human cells
0:12:21 and the cells that we use.
0:12:25 So right now, human site has banks of human cells.
0:12:27 And in fact, we have enough cells banked
0:12:31 to support tissue production for the next 30 or 40 years.
0:12:32 We’ve got a lot of cells.
0:12:35 But where those cells come from
0:12:39 is actually they come from organ and tissue donors.
0:12:43 So if a patient dies and they become an organ donor,
0:12:44 their heart might go somewhere
0:12:47 and their liver might go somewhere else.
0:12:50 But there’s actually no transplantation use
0:12:52 for their blood vessels.
0:12:56 So we worked with organ procurement organizations
0:12:59 and we obtained consent from donor families.
0:13:03 And we obtained large blood vessels, aorta’s,
0:13:06 from hundreds of different organ donors.
0:13:08 We isolated cells from those donors
0:13:12 and then we did a tremendous amount of screening
0:13:15 to identify which cells would really be optimal
0:13:17 for growing new arteries.
0:13:19 And then we established banks.
0:13:23 So actually we have banks of donor cells now
0:13:25 that are derived from organ donors.
0:13:28 – So it’s like vials of cells in fluid
0:13:31 in the refrigerator or something like that?
0:13:34 – It’s vials of cells stored in liquid nitrogen.
0:13:36 So they’re extremely cold.
0:13:39 But that means that the cells can store for decades.
0:13:42 Okay, so very good.
0:13:47 That’s step one, get a lot of nice, healthy aorta cells.
0:13:51 And just to be clear, by the way,
0:13:55 are blood vessel cells the same in all of the vessels?
0:13:57 Dumb question, but are the cells of the aorta the same
0:14:00 as the cells in whatever other blood vessel?
0:14:03 – The cells, even within your aorta,
0:14:05 there’s different flavors of cells.
0:14:08 And the cells differ between arteries and veins
0:14:11 and big arteries and small arteries and capillaries.
0:14:14 So that was really part of the challenge for us,
0:14:17 was really identifying which subset
0:14:21 of cells in the aortas was really the most productive
0:14:25 for growing new arteries.
0:14:28 As it turns out, some of the cells in your body,
0:14:30 even if you’re an older person,
0:14:34 still have this sort of progenitor or stem-like capability.
0:14:38 And those cells we found could grow extensively
0:14:42 in our process and could grow large numbers of new arteries.
0:14:46 – Great, so you got not only a lot of cells,
0:14:48 you got a lot of the right kind of cells.
0:14:50 What do you do with them?
0:14:52 – Well, when we want to grow a batch of arteries,
0:14:56 right now we grow 200 arteries at a time
0:14:59 in a highly automated system that we’ve designed
0:15:02 and built over many years.
0:15:03 – Artery factory.
0:15:06 – It’s an artery factory, yes, yes.
0:15:10 In fact, we have eight installed units now.
0:15:13 Each unit, which we call a Luna 200 unit,
0:15:15 can grow 200 vessels at a time.
0:15:17 – And a unit is like a machine?
0:15:18 – It’s a machine, it’s a machine.
0:15:20 It’s about as big as a school bus.
0:15:21 – Okay.
0:15:24 – And it’s essentially a large incubator
0:15:28 where we control temperature and humidity and oxygen.
0:15:31 But we also have inside the school bus,
0:15:35 inside the incubator, we have bioreactor systems
0:15:39 where we can provide an environment
0:15:41 for the cells while they’re growing
0:15:46 so that the cells form new arteries.
0:15:48 But I’m sort of jumping ahead a little bit.
0:15:50 So when we start a batch,
0:15:53 what we do is we take a tiny vial of cells,
0:15:55 it’s about a fifth of a teaspoon.
0:15:57 It’s a little tiny volume.
0:16:00 And we thaw out those cells and then we grow them.
0:16:05 And we let them expand about 2000 fold.
0:16:06 – Okay.
0:16:09 – And then we gather all those cells
0:16:12 and then we essentially walk over
0:16:16 to one of our production units, one of our Luna 200s.
0:16:21 And in the Luna 200 is 200, what we call bioreactor bags.
0:16:27 Each bag has a scaffold inside of it that’s sterile.
0:16:32 And that scaffold is six millimeters in diameter
0:16:33 and 40 centimeters long.
0:16:36 So that’s the size of the artery we grow.
0:16:39 – So it’s made of like plastic or something?
0:16:41 – It’s a degradable plastic.
0:16:44 It’s actually, it’s the same material
0:16:47 that’s used in degradable sutures.
0:16:50 So each fiber is about the width of a cell.
0:16:53 And there’s a lot of empty space in between the fibers.
0:16:57 But the shape of the scaffold,
0:17:01 we can shape it into this six millimeter diameter tube
0:17:03 that’s 40 centimeters long.
0:17:06 And what we do is we take the cells that we grew
0:17:08 and we inject them into the bag.
0:17:13 And the cells stick onto the fibers of the scaffold.
0:17:16 It’s like a person hanging onto a metal pole
0:17:19 on building scaffolding.
0:17:21 If you think of it, that’s kind of what it’s like.
0:17:23 – And so the cells are grabbing sort of all over
0:17:26 this little plastic tube all over the scaffold.
0:17:30 – Yes, each cell grabs onto a metal pole
0:17:32 and they hang on for dear life.
0:17:37 And then we basically fill the bag,
0:17:39 the bioreactor bag with culture medium.
0:17:42 And then that culture medium is super secret.
0:17:44 It has lots of yummy stuff in it
0:17:47 that convinces the cells to grow.
0:17:50 And while they’re growing, they secrete proteins
0:17:54 like collagen and other matrix molecules.
0:17:57 What also happens while the cells are growing
0:18:01 in the culture medium is we’ve designed the bioreactor bag
0:18:03 so that we can stretch the cells
0:18:07 as if the cells are in the wall of an artery
0:18:09 and they’re feeling your heartbeat.
0:18:13 – Ah-ha, because arteries need to get wider
0:18:16 and get narrower as the pulse of blood comes in and out.
0:18:17 – Yes, yes.
0:18:17 So if you put your–
0:18:18 – It’s like why there’s two different numbers
0:18:20 in your blood pressure reading.
0:18:23 – Exactly, there’s a higher pressure and a lower pressure.
0:18:25 And if you put your finger on your wrist,
0:18:27 you can feel your pulse.
0:18:29 That pulse is your artery distanding
0:18:33 and then recoiling every time your heart beats.
0:18:35 Well, it turns out we learned very early.
0:18:38 We figured out when I was working in Langer’s lab
0:18:41 in the ’90s that if we didn’t stretch these cells
0:18:44 while they were growing, they didn’t really make an artery
0:18:46 ’cause they didn’t know they were supposed to do that.
0:18:48 – So they would be too rigid.
0:18:49 They wouldn’t be able to–
0:18:52 – They would be disorganized, actually.
0:18:54 They would just grow randomly
0:18:56 ’cause they didn’t know what they were supposed to be doing.
0:19:01 – So it’s like that pulse kind of tells them
0:19:03 how to grow and organize themselves.
0:19:04 – Yes, absolutely.
0:19:05 – Ah, it’s really interesting.
0:19:06 – It’s really interesting, yeah.
0:19:09 – So how do you, so you do that in the bag?
0:19:10 How do you get them to–
0:19:11 – Yes.
0:19:13 – So you have a little sort of imitation heartbeat
0:19:14 sort of in the bag?
0:19:18 – We have a little imitation heartbeat in the bag, yes.
0:19:21 And every vessel gets stretched the same amount
0:19:24 and they get stretched cyclically by this heartbeat
0:19:26 for the entire two-month culture duration.
0:19:30 – So they spend two months growing
0:19:34 and learning how to be cells in an artery
0:19:39 and filling in all the spaces on the scaffold,
0:19:41 on the little plastic tube.
0:19:43 What happens at the end of that two months?
0:19:44 – Well, at the end of the two months,
0:19:45 a couple things have happened.
0:19:50 One is that scaffolding, which I said is degradable,
0:19:54 has mostly degraded, so it’s pretty much all gone.
0:19:58 So what we have by that time is a human artery
0:20:03 that has these cells and also the collagen matrix proteins
0:20:06 that they made, and there’s really no scaffold left.
0:20:12 So in a final step, we drain out the culture medium
0:20:15 that we use to convince the cells to grow
0:20:19 and then we replace it with detergents.
0:20:23 And we basically, we spend five days
0:20:26 and we wash the cells out of the artery.
0:20:29 – Huh, so after two months when you take it out,
0:20:33 it feels like it’s a lot like an artery in my body,
0:20:35 in your body, in anybody’s body.
0:20:39 But that’s not good because if you put that in a patient,
0:20:42 you’ll have a bad immune response.
0:20:45 That’s presumably the problem, why you can’t just use that.
0:20:46 – That’s the reason, yes.
0:20:49 Because again, these are cells from a cell bank.
0:20:52 So if I grow that artery and then I implant it in you,
0:20:54 your body will reject it.
0:20:55 ‘Cause it’s a transplant. – It’s a transplant.
0:20:57 And suddenly I’m getting a transplant.
0:21:02 And so what is that final step or that next step?
0:21:06 – So the final step, we call that decellularization.
0:21:09 So we rinse away the cells,
0:21:13 which are really the part that creates the immune rejection.
0:21:16 But what we leave behind and what we’re very careful
0:21:20 not to disturb is the extracellular matrix proteins,
0:21:22 like the collagen that I mentioned.
0:21:25 There’s actually 40 or 50 proteins there.
0:21:28 The reason that’s important is because it’s really
0:21:32 the collagen and the proteins that give the vessel
0:21:35 all of its mechanical properties.
0:21:38 So actually washing the cells out of the tissue
0:21:40 doesn’t change how strong it is.
0:21:43 It’s still just as strong as your arteries
0:21:45 after we wash the cells out.
0:21:48 The cells are really there to be little protein factories.
0:21:49 – Yeah, right.
0:21:51 – But they themselves are not very strong.
0:21:56 But because collagen is so important,
0:21:59 like for example, your collagen and my collagen
0:22:01 are identical.
0:22:02 They’re identical.
0:22:03 – You’re saying there’s no kind of,
0:22:06 there’s no potential immune response.
0:22:07 It’s just protein.
0:22:09 It’s just these exact same protein.
0:22:10 You couldn’t tell the difference.
0:22:12 You couldn’t tell who it came from.
0:22:14 – Yes, your body can’t tell the difference.
0:22:18 And so we’ve implanted these decelularized,
0:22:22 engineered arteries into nearly 600 patients
0:22:23 over the last 11 years.
0:22:26 We’ve never seen a single episode of rejection.
0:22:30 – Because in an immune sense, there’s nothing to reject.
0:22:32 – That’s what we believe, yes.
0:22:36 – So now it’s like kind of like a dead artery,
0:22:40 an artery without any personality, a generic artery.
0:22:47 You put it in a person, in a patient, what happens then?
0:22:49 – Well, there’s a couple of things that happen.
0:22:51 The first thing that happens is that the artery
0:22:52 works as it should.
0:22:57 So the main job of arteries is to conduct blood flow
0:22:59 so that you can get blood from point A to point B.
0:23:02 So that happens as soon as the surgeon sows it in
0:23:04 and takes the clamps off.
0:23:07 So some people worry, gee, we wash the cells out,
0:23:09 will it be leaky?
0:23:11 That doesn’t happen.
0:23:12 We don’t see that.
0:23:18 But what’s probably cooler is that over time,
0:23:23 cells from the patient see this naked artery
0:23:25 and to them, it sort of looks like
0:23:27 an empty apartment building.
0:23:31 And what we’ve seen happen, in fact, we’ve published this,
0:23:36 is that cells from the patient migrate into the
0:23:42 acellular artery and they start off being progenitor cells,
0:23:44 but they become vascular cells.
0:23:49 So over a period of months, this non-living thing becomes
0:23:52 a living artery and it’s the patient’s own.
0:23:55 So this is really, I think,
0:23:58 this is regenerative medicine in the truest sense.
0:24:03 – So can you tell the difference, whatever,
0:24:05 a year later between the section of artery
0:24:08 that you put in and the patient’s own artery?
0:24:10 – You can tell differences.
0:24:12 There are still subtle differences.
0:24:16 There is one stretchy protein called elastin,
0:24:18 which is in all of our arteries,
0:24:21 but the engineered arteries don’t have elastin,
0:24:24 so that’s actually the easiest way to tell.
0:24:28 Aside from that, there’s not a lot of differences.
0:24:32 – Does the absence of elastin make a functional difference?
0:24:34 – It doesn’t seem to.
0:24:37 – This is something that I used to worry about
0:24:40 as a younger professor 10, 15, 20 years ago,
0:24:44 but over 1,000 patient years of exposure
0:24:46 tells us that it probably doesn’t matter.
0:24:50 – It’s weird that there’s a thing in our arteries
0:24:51 that we could do without.
0:24:53 You’d think that would, you know,
0:24:56 the way fish that live in caves for a million years
0:24:59 don’t have eyes anymore because it’s costly to have eyes
0:25:01 and if you don’t need them, they evolve away.
0:25:03 – Well, I think that’s the difference
0:25:06 between having no elastin in your body,
0:25:10 but having or not having elastin just in a short segment.
0:25:13 So if you have no elastin in your whole body,
0:25:17 that makes life very, very hard for your heart.
0:25:19 However, if it’s just a short segment
0:25:22 of the vessels in your body that don’t have elastin,
0:25:24 your heart doesn’t care too much.
0:25:27 (upbeat music)
0:25:28 – We’ll be back in a minute.
0:25:31 (upbeat music)
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0:26:25 – Laura’s company, Humasite,
0:26:28 applied late last year for FDA approval.
0:26:29 They expect to hear back this summer.
0:26:32 And she told me about the evidence
0:26:34 that made her think, that made the company think,
0:26:38 that they were finally ready to apply for FDA approval
0:26:42 for widespread use of these vessels they’re creating.
0:26:46 – So the trial that is supporting our current application
0:26:50 at the FDA was conducted at 19 trauma centers
0:26:52 in the U.S. and Israel.
0:26:55 And we treated a total of 70 patients
0:26:59 who had all sorts of injuries.
0:27:01 You know, car accidents, gunshot wounds,
0:27:03 industrial accidents.
0:27:05 We treated a guy who worked on a farm
0:27:07 who was crushed by a cow.
0:27:10 We treated a woman who was crushed by a crane on a dock.
0:27:14 I mean, we just all sorts of terrible injuries.
0:27:16 And then we followed those patients.
0:27:18 Many of them were still following.
0:27:21 But it was really the data from that pivotal trial
0:27:26 that showed really excellent outcomes in terms of safety
0:27:30 but also in terms of how well blood flow was restored
0:27:34 and a very low number of amputations and infections.
0:27:38 So seeing all of that clinical data together
0:27:40 from this pivotal trial
0:27:42 and then combined with the Ukraine experience
0:27:45 because the Ukraine humanitarian effort
0:27:48 was ongoing at the same time we were doing this pivotal trial.
0:27:51 So putting all of that information together
0:27:53 is what really formed the basis
0:27:56 of our filing with the FDA last year.
0:28:00 – You mentioned that there are other options.
0:28:04 Where do your arteries fit in the sort of,
0:28:06 you know, comparative landscape?
0:28:08 Like when is something else better
0:28:10 and when is one of your arteries better?
0:28:12 – Well, this is something that, you know,
0:28:16 the FDA would argue is probably their decision to make.
0:28:18 Our argument is that in patients
0:28:22 who don’t have their own vein available
0:28:23 and for injured patients,
0:28:26 it may be because their limbs are injured.
0:28:30 It may be because the need to restore blood flow
0:28:34 is so acute that the surgeons don’t have that extra hour
0:28:35 to harvest the vein.
0:28:37 It could be that the surgeon doesn’t wanna
0:28:39 injure the patient further.
0:28:42 So in patients in whom vein is not feasible,
0:28:48 our argument is that the HAV is an excellent option.
0:28:53 And our data showed when we compared our outcomes
0:28:58 to outcomes of patients who are treated with plastic graphs,
0:29:02 like made out of Teflon, in trauma,
0:29:04 our data showed that our outcomes
0:29:08 are substantially better than plastic graphs.
0:29:11 – What are some of the next things that you’re working on?
0:29:14 Like what are you trying to figure out now?
0:29:16 – Well, on the clinical side,
0:29:19 we have trials that are under ways
0:29:21 that we’re still collecting data on
0:29:23 in patients with kidney failure,
0:29:26 who were studying our engineered vessels
0:29:32 as what we call a dialysis access,
0:29:35 which is where our vessels are sewn into the patient’s arm
0:29:37 between an artery and a vein.
0:29:41 And then that vessel is used in the dialysis clinic
0:29:44 where nurses poke needles into the vessel
0:29:47 and use that so the patient can get dialysis.
0:29:50 So we’re studying that indication.
0:29:53 And in fact, we have another pivotal trial
0:29:56 that we expect to read out in the third quarter of this year
0:30:01 in 2024 that will tell us if the HAV works better
0:30:07 in dialysis than basically the gold standard,
0:30:09 which is where a surgeon sews an artery
0:30:11 and a vein together directly.
0:30:13 – So that’s the kind of short-term future
0:30:18 it’s basically trying to get the dialysis-related indication.
0:30:21 When you think more long-term,
0:30:24 if you think, I don’t even know how many years that is for you.
0:30:26 Is it five years? Is it 10 years?
0:30:28 Like what do you think about?
0:30:29 – So for the last several years,
0:30:32 we’ve been making smaller diameter vessels
0:30:35 that are the right size for heart bypass.
0:30:39 And we’ve actually been testing
0:30:41 these three and a half millimeter vessels
0:30:45 doing heart bypasses in primates,
0:30:48 non-human primates and other large animals.
0:30:51 And we’re collecting long-term data
0:30:56 to submit as a file to the FDA in order to gain approval
0:30:59 to do a phase one trial in patients who need a heart bypass
0:31:04 but who don’t have their own vein to do the bypass.
0:31:08 So we would hope to start that first in human trial
0:31:11 in heart bypass in the next couple of years.
0:31:13 So bypass is a, you know,
0:31:17 unfortunately wildly common procedure.
0:31:20 My dad had one, my grandfather had a few.
0:31:23 I’m taking statins and running all the time
0:31:25 in hopes that I’ll dodge that bullet, but who knows?
0:31:29 So presumably that would be a very large market.
0:31:33 I mean, it’s also the case that many patients
0:31:35 are able to use their own veins.
0:31:37 You mentioned, you’re thinking about patients who can’t.
0:31:40 In what instances are graphs unavailable
0:31:41 for patients getting bypass?
0:31:43 And what do doctors do now in those instances?
0:31:46 – Well, there’s lots of situations
0:31:50 where patients who need a vein for heart bypass don’t have it.
0:31:52 So for example, if you have varicose veins,
0:31:56 if your veins are very dilated, surgeons can’t use them.
0:32:01 In the modern era, vein clinics are
0:32:03 sclerosing people’s veins all the time.
0:32:08 So that ladies can have beautiful legs at the beach,
0:32:10 which is great in the short term,
0:32:11 but not so good in the long term.
0:32:14 And then lastly, as we know,
0:32:18 there’s a growing obesity and diabetes epidemic
0:32:21 in the United States, most of the Western world.
0:32:23 For those patients, if you cut into their legs
0:32:25 and take their vein out,
0:32:27 they have a higher rate of complications.
0:32:31 Their incisions don’t heal, they get infected.
0:32:32 They have all sorts of problems.
0:32:35 – Are there not Teflon artificial veins
0:32:37 that can be used for bypass?
0:32:40 – There’s nothing artificial
0:32:44 that works for those smaller diameter vessels in your heart.
0:32:50 Despite a huge need, there simply isn’t anything.
0:32:53 – So you said that when you started out 25, 30 years ago,
0:32:56 making a connective tissue like blood vessels,
0:32:57 like what you’re doing,
0:33:00 seemed much easier than making solid organs.
0:33:02 And so I’m curious after all this time
0:33:04 and all the advancements there have been,
0:33:07 does making a solid organ in a lab
0:33:09 still feel wild hard?
0:33:13 – It’s still wild hard,
0:33:16 but it’s starting to feel tractable.
0:33:19 So one of the parts that we haven’t talked about is,
0:33:22 I’ve had this dual life for many years as a,
0:33:24 right now I’m the CEO of Humasite
0:33:26 and I’m not an academic anymore,
0:33:30 but for many years I sort of had one foot in academia
0:33:32 and one foot in my company.
0:33:36 And while I was working as a professor at Yale,
0:33:39 we were the first lab to actually be able
0:33:44 to grow engineered lungs and implant them in rats
0:33:47 and showed that they could exchange gas for a few hours.
0:33:52 So we have a pathway, I believe,
0:33:56 to growing more complex tissues, lungs in particular.
0:34:00 And in fact, some of my former trainees from my lab
0:34:03 are off-scattered at different institutions
0:34:05 working on that problem right now.
0:34:08 – On lab-grown lungs in particular?
0:34:09 – Lab-grown lungs, yes.
0:34:13 – Are lungs less complex than other organs?
0:34:15 Is that why lungs?
0:34:19 – Lungs are not less complex,
0:34:21 but lungs, interestingly,
0:34:23 they’re the only organ in your body
0:34:26 that’s mostly empty space.
0:34:29 And in biology, in biotechnology,
0:34:32 we’re very good at growing thin layers of cells
0:34:36 or monolayers or thin collections of cells.
0:34:38 One of the things that we did figure out
0:34:41 in my academic lab is that
0:34:45 instead of using a plastic scaffold for lungs,
0:34:50 what we can probably do is take a native lung,
0:34:55 either a human lung or maybe a primate lung or a pig lung,
0:35:00 and decelularize that lung and use that as a scaffold.
0:35:03 In that case, we could maybe take stem cells
0:35:07 from the patient and repopulate that scaffold
0:35:09 that has all of the structure of the lung,
0:35:11 all the air sacs, all the blood vessels,
0:35:14 all of that important lung structure.
0:35:17 If we can repopulate that with cells,
0:35:20 then we’re basically, we kind of have a leg up,
0:35:22 we’ve got the lung structure to start with,
0:35:25 and then we just repopulate it with cells from the patient,
0:35:28 and then we’ve got a designer organ.
0:35:32 (upbeat music)
0:35:34 We’ll be back in a minute with the lightning round.
0:35:47 So I’m cognizant of the time.
0:35:52 I just wanna ask you some lightning round questions
0:35:53 to finish.
0:35:57 They will be slightly more random
0:35:59 than the questions I’ve asked you so far.
0:36:04 What’s one thing you learned from Bob Langer?
0:36:08 – I learned from Bob Langer
0:36:11 that time is the one thing you can’t get back,
0:36:18 that getting things done cost effort
0:36:20 and they cost money and they cost time.
0:36:25 You can get more effort and you can get more money,
0:36:26 but you can’t get more time.
0:36:31 So he was always focused on finding the most efficient way
0:36:35 to get something done that took the least amount of time
0:36:38 because as it turns out, everything takes longer
0:36:39 than you think it’s gonna.
0:36:44 – It’s interesting to think about him that way, right?
0:36:45 ‘Cause I interviewed him and I was like,
0:36:48 how did you do so many things?
0:36:50 And he, I don’t know if he knew,
0:36:52 but like that answer that you just gave
0:36:55 is a pretty good answer for how he did so many things.
0:37:00 So it was what the mid 90s is that right?
0:37:05 When you started sort of getting into regenerative medicine.
0:37:09 And I’m curious, you know, that’s 30 years ago now.
0:37:14 And I’m curious, looking back now,
0:37:17 it’s sort of what you thought then,
0:37:18 what is something that’s progressed
0:37:21 more quickly than you thought it would?
0:37:23 – Tools.
0:37:26 Tools.
0:37:30 One of the reasons that cell therapy
0:37:32 and regenerative medicine is taking off now
0:37:35 and will continue to just explode
0:37:38 in the next couple of decades is tools.
0:37:41 We can look at a tissue that we’re growing
0:37:47 and sort of generate sort of a report card of,
0:37:51 here’s how the cells are behaving,
0:37:53 you know, 15% of the cells are behaving correctly,
0:37:57 85% of the cells are not doing what they’re supposed to do.
0:37:59 And I can compare that report card
0:38:00 to what a native tissue looks like.
0:38:03 And then I can go back and fix what I’m doing
0:38:06 on the engineered side and just iterate that way.
0:38:07 It allows you to make a roadmap.
0:38:10 – What’s something that has progressed more slowly
0:38:11 than you would have thought?
0:38:18 – I think that the development
0:38:22 of functional connective tissues
0:38:25 has progressed more slowly than I would have thought.
0:38:26 – The thing you do?
0:38:28 – The thing I do.
0:38:29 The thing I do.
0:38:32 And I’m surprised at that.
0:38:36 If we look, so as I said, in the 1990s,
0:38:40 there were approved versions of tissue engineered cartilage
0:38:42 and tissue engineered skin
0:38:44 that were on the market in the US or Europe.
0:38:46 – Did those just turn out to be way easier
0:38:48 than everything else or what?
0:38:50 – They are, they’re easier.
0:38:52 The tissues are simpler.
0:38:57 And what we would say are design requirements
0:38:59 are a little bit less stringent.
0:39:03 So what has progressed more slowly than I would have thought
0:39:06 is making tissues that have tougher design criteria
0:39:09 and doing that successfully.
0:39:12 – Seems like you’re almost there.
0:39:15 – We’re almost there.
0:39:17 But it does, I’ve been working on it for 30 years.
0:39:18 It does take time.
0:39:22 – Did you feel like you were almost there 10 years ago?
0:39:24 – I felt like I was almost there 20 years ago.
0:39:27 (laughing)
0:39:29 – But this time you mean it.
0:39:30 – This time I mean it.
0:39:35 But no, I think it’s to make tissues,
0:39:39 you have to understand the cell biology
0:39:42 and that single cell information that I mentioned.
0:39:44 But you also really have to come to grips
0:39:48 with what the tissue does and what characteristics
0:39:50 the whole tissue must have in order to function.
0:39:54 And that’s a complicated set of problems.
0:39:57 And it takes, one person can’t do it all.
0:39:59 It takes a really terrific team working on it
0:40:01 for a long time.
0:40:03 – Do you think that having a founding team
0:40:06 that was all women affected the culture of the company?
0:40:09 – It affected a lot of things.
0:40:11 It affected the culture of the company.
0:40:17 Humasite has never suffered from a sense
0:40:19 that women can’t be heard in a meeting.
0:40:24 It’s actually allowed us to attract and retain
0:40:26 incredibly smart and high powered women
0:40:28 because they know they will never have to fight
0:40:30 that uphill battle.
0:40:33 So it actually gives us an edge in terms of recruitment.
0:40:37 But in retrospect, now having been at this
0:40:41 for nearly 20 years, I would say that in the early years,
0:40:44 I think it made it harder for us to raise money.
0:40:49 People write about this and people used to ask me
0:40:52 about it early on and I sort of discarded it
0:40:54 as being paranoid.
0:40:58 But now looking back, I think it hurt us.
0:41:02 I just think that people, there’s an expectation that,
0:41:04 well, if this is an all women company,
0:41:07 then maybe this isn’t gonna work.
0:41:09 – What’s one thing you wish more people understood
0:41:10 about cells?
0:41:18 – I wish that people appreciated how smart cells are.
0:41:19 – What do you mean?
0:41:25 – Well, what I’ve learned is that if I work
0:41:30 with the right starting cells, if I give them
0:41:35 about eight cues, not one cue, but it’s not 1,000 cues.
0:41:38 If I give them about eight cues,
0:41:40 couple of the right growth factors,
0:41:44 right amount of stretch, right temperature,
0:41:48 right oxygen level, if I give them about eight cues,
0:41:50 they take it and run with it.
0:41:53 And without any supervision from me,
0:41:56 they make a brand new artery that looks and feels
0:41:57 like the real thing.
0:42:01 And that’s a remarkable amount of intelligence
0:42:03 inside a little tiny cell.
0:42:06 So our cells are very self-directed.
0:42:08 They’re very smart.
0:42:11 And in order to coax them to make spare parts,
0:42:14 we just have to figure out what that right handful
0:42:15 of cues is.
0:42:18 (upbeat music)
0:42:21 – Lauren Nicholson is the co-founder
0:42:22 and CEO of Humasite.
0:42:26 Today’s show was produced by Gabriel Hunter-Chang.
0:42:29 It was edited by Lydia Jean-Cott
0:42:31 and engineered by Sarah Brugger.
0:42:35 You can email us at problem@pushkin.fm.
0:42:37 I’m Jacob Goldstein and we’ll be back next week
0:42:39 with another episode of What’s Your Problem?
0:42:41 (upbeat music)
0:42:44 (upbeat music)
0:42:47 (upbeat music)
0:42:57 [BLANK_AUDIO]
Laura Niklason is the co-founder and CEO of Humacyte. Laura’s problem is this: How can you use human cells to create blood vessels that surgeons can pull out of a bag and implant into patients? Although still awaiting FDA approval in the U.S., Humacyte’s vessels have already been used to treat wounded soldiers in Ukraine.
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