1 00:00:15,356 --> 00:00:22,196 Speaker 1: Pushkin. When the war in Ukraine broke out a few 2 00:00:22,276 --> 00:00:26,876 Speaker 1: years ago, Laura Nicholson started hearing from Ukrainian doctors who 3 00:00:26,916 --> 00:00:29,756 Speaker 1: were treating soldiers at frontline hospitals. 4 00:00:29,676 --> 00:00:33,356 Speaker 2: When patients would present to the hospital. In many cases, 5 00:00:33,476 --> 00:00:37,476 Speaker 2: these were soldiers who had been injured in the war, 6 00:00:37,716 --> 00:00:41,916 Speaker 2: typically with blast injuries and shrapnel injuries, because you know, 7 00:00:42,076 --> 00:00:45,436 Speaker 2: ied explosions are really one of the you know, that's 8 00:00:45,516 --> 00:00:49,196 Speaker 2: modern warfare. People lose limbs, and one of the reasons 9 00:00:49,236 --> 00:00:52,676 Speaker 2: they lose limbs is because the blood flow gets damaged 10 00:00:52,716 --> 00:00:55,756 Speaker 2: and cut off, and it's very hard to restore that 11 00:00:55,796 --> 00:00:59,636 Speaker 2: blood flow, especially since the wounds are very contaminated. That 12 00:01:00,156 --> 00:01:04,076 Speaker 2: these these limbs are filled with shrapnel and metal and soil, 13 00:01:04,276 --> 00:01:07,196 Speaker 2: and it's just it's very horrific. 14 00:01:07,236 --> 00:01:10,116 Speaker 1: In some cases, the doctors were getting in touch with 15 00:01:10,196 --> 00:01:13,396 Speaker 1: Laura because she and her colleagues had spent more than 16 00:01:13,436 --> 00:01:16,956 Speaker 1: twenty years figuring out how to use human cells to 17 00:01:17,036 --> 00:01:21,436 Speaker 1: create new blood vessels outside the human body. The idea 18 00:01:21,676 --> 00:01:24,316 Speaker 1: is to create a supply of vessels that surgeons can 19 00:01:24,436 --> 00:01:28,076 Speaker 1: have on hand to implant into patients. She calls these 20 00:01:28,156 --> 00:01:33,876 Speaker 1: vessels havs, or human acellular vessels. The havs have not 21 00:01:34,036 --> 00:01:38,036 Speaker 1: yet been approved by the FDA, but the Ukrainian surgeons 22 00:01:38,076 --> 00:01:40,956 Speaker 1: thought they would be helpful, so after getting approval from 23 00:01:40,996 --> 00:01:44,276 Speaker 1: the Ukrainian Ministry of Health, Laura and her colleagues sent 24 00:01:44,556 --> 00:01:47,956 Speaker 1: havs to several frontline hospitals in Ukraine. 25 00:01:48,156 --> 00:01:53,036 Speaker 2: So when these patients would present to the hospital, if 26 00:01:53,076 --> 00:01:56,996 Speaker 2: the surgeon felt that the best treatment for that patient 27 00:01:57,196 --> 00:02:00,996 Speaker 2: was using the engineered vessel to rapidly restore blood flow, 28 00:02:01,476 --> 00:02:04,516 Speaker 2: he would do that. And so that means, you know, 29 00:02:05,436 --> 00:02:07,996 Speaker 2: cleaning out the wound. You know, the patients asleep at 30 00:02:07,996 --> 00:02:10,676 Speaker 2: this time, and they're having other injuries fixed as well, 31 00:02:11,556 --> 00:02:15,636 Speaker 2: but cleaning out the wound, isolating the damaged artery and 32 00:02:15,676 --> 00:02:19,236 Speaker 2: then replacing the damage segment with our engineered vessel. 33 00:02:19,676 --> 00:02:20,516 Speaker 1: And how did it go? 34 00:02:21,796 --> 00:02:26,156 Speaker 2: Well? The outcomes in Ukraine went very well. We treated 35 00:02:26,156 --> 00:02:30,516 Speaker 2: a total of nineteen patients over a year long humanitarian effort, 36 00:02:30,876 --> 00:02:34,356 Speaker 2: and in fact we're still following those patients now. But 37 00:02:34,476 --> 00:02:37,196 Speaker 2: what we found is that in the first month, which 38 00:02:37,236 --> 00:02:40,916 Speaker 2: is really the most important time after somebody gets injured, 39 00:02:41,036 --> 00:02:43,756 Speaker 2: it's how things go in the first month. What we 40 00:02:43,836 --> 00:02:47,116 Speaker 2: found in the first month is that of the nineteen 41 00:02:47,156 --> 00:02:52,396 Speaker 2: patients we treated. Every single limb was salvaged. There was 42 00:02:52,476 --> 00:02:54,916 Speaker 2: no loss of limb, there was no loss of life. 43 00:02:55,796 --> 00:02:58,356 Speaker 2: And this is true even though some of the patients 44 00:02:58,396 --> 00:03:01,036 Speaker 2: we treated were very badly injured. And in fact, one 45 00:03:01,076 --> 00:03:03,916 Speaker 2: of the patients, the surgeon told us later that he 46 00:03:04,036 --> 00:03:08,236 Speaker 2: was quite sure this man would die, but he survived 47 00:03:08,316 --> 00:03:10,436 Speaker 2: and he walked out of the hospital on his own leg. 48 00:03:11,116 --> 00:03:15,716 Speaker 2: So I believe in my heart that there are soldiers 49 00:03:15,716 --> 00:03:19,076 Speaker 2: in Ukraine who are walking and breathing now who would 50 00:03:19,076 --> 00:03:20,716 Speaker 2: not be if it weren't for the AHAV. 51 00:03:26,916 --> 00:03:29,436 Speaker 1: I'm Jacob Goldstein and this is What's Your Problem, the 52 00:03:29,476 --> 00:03:31,596 Speaker 1: show where I talk to people who are trying to 53 00:03:31,636 --> 00:03:36,476 Speaker 1: make technological progress. My guest today is Laura Nicholson. She's 54 00:03:36,556 --> 00:03:40,396 Speaker 1: the co founder and CEO of Humo site. Laura's problem 55 00:03:40,516 --> 00:03:43,676 Speaker 1: is this, can you use human cells to create a 56 00:03:43,676 --> 00:03:47,076 Speaker 1: blood vessel that is better, at least for some patients 57 00:03:47,356 --> 00:03:51,556 Speaker 1: than any other options available today. Laura has both a 58 00:03:51,596 --> 00:03:55,436 Speaker 1: PhD and an MD. She's worked as a physician in 59 00:03:55,476 --> 00:03:58,796 Speaker 1: the intensive care unit. So to start, I asked her 60 00:03:58,916 --> 00:04:01,236 Speaker 1: how she got into the blood vessel business in the 61 00:04:01,276 --> 00:04:01,836 Speaker 1: first place. 62 00:04:03,716 --> 00:04:07,636 Speaker 2: Well, you know, I started working trying to grow arteries 63 00:04:07,676 --> 00:04:12,196 Speaker 2: from scratch. In the mid nineteen nineties, I was training 64 00:04:12,516 --> 00:04:16,156 Speaker 2: for my residency at mass General Hospital. I was taking 65 00:04:16,196 --> 00:04:19,116 Speaker 2: care of patients in the operating room. I was an 66 00:04:19,156 --> 00:04:23,356 Speaker 2: antithesiologist and an intensive care unit doctor, and I took 67 00:04:23,396 --> 00:04:26,356 Speaker 2: care of a lot of patients who had vascular disease 68 00:04:26,436 --> 00:04:29,756 Speaker 2: in their heart or their legs or elsewhere. And you know, 69 00:04:30,156 --> 00:04:34,876 Speaker 2: diseases of arteries are still the biggest killers of people 70 00:04:34,916 --> 00:04:37,876 Speaker 2: in the Western world, more so than cancer, more so 71 00:04:37,956 --> 00:04:38,796 Speaker 2: than anything else. 72 00:04:38,956 --> 00:04:41,596 Speaker 1: Right, Sometimes we call it heart disease, right, but it's 73 00:04:41,636 --> 00:04:46,356 Speaker 1: cardiovascular disease. And the vascular piece there is vessels, right. 74 00:04:46,516 --> 00:04:49,756 Speaker 2: Yes, So it can be any artery supplying any part 75 00:04:49,796 --> 00:04:53,956 Speaker 2: of your body, and when those fail or clot or 76 00:04:54,996 --> 00:04:59,076 Speaker 2: dilate or become infected, they need to be bypassed or replaced. 77 00:04:59,156 --> 00:05:04,236 Speaker 2: And it's a universal thing in all of healthcare. And 78 00:05:04,276 --> 00:05:09,836 Speaker 2: what I learned during my training is that typically when 79 00:05:09,836 --> 00:05:13,516 Speaker 2: we need to repair or replace an artery, we rob 80 00:05:13,596 --> 00:05:17,036 Speaker 2: Peter to pay Paul. In other words, we cut open 81 00:05:17,076 --> 00:05:19,636 Speaker 2: one part of your body and take a vein out 82 00:05:19,716 --> 00:05:21,636 Speaker 2: or an artery out, and then we move it over 83 00:05:21,796 --> 00:05:25,196 Speaker 2: and use that vein or artery to repair the artery 84 00:05:25,236 --> 00:05:26,276 Speaker 2: that's broken. 85 00:05:26,316 --> 00:05:29,916 Speaker 1: Like the classic as somebody's getting a bypass surgery for 86 00:05:29,996 --> 00:05:32,356 Speaker 1: the blood vessels around their heart, and the surgeon takes 87 00:05:32,436 --> 00:05:34,916 Speaker 1: vessels from their leg, right, you take vessels from the 88 00:05:34,956 --> 00:05:36,596 Speaker 1: thid and you put it next to the heart. 89 00:05:37,516 --> 00:05:42,916 Speaker 2: Yes, yes, And as you might imagine, that always injures 90 00:05:42,956 --> 00:05:45,356 Speaker 2: the patient in the process of trying to fix the patient. 91 00:05:46,036 --> 00:05:50,236 Speaker 2: But importantly, not everybody has veins and arteries hanging around 92 00:05:50,276 --> 00:05:53,396 Speaker 2: in their body that are spare, that are the right 93 00:05:53,556 --> 00:05:56,556 Speaker 2: quality and the right size and shape to fix the 94 00:05:56,636 --> 00:06:00,916 Speaker 2: problem at hand. And when that happens, surgeons are forced 95 00:06:00,956 --> 00:06:04,316 Speaker 2: to use plastic tubes, tubes made out of teflon, for example. 96 00:06:05,036 --> 00:06:07,396 Speaker 2: And as you might imagine, if you sew a teflon 97 00:06:07,516 --> 00:06:11,516 Speaker 2: tube into your vein ascular system, that often doesn't work 98 00:06:11,676 --> 00:06:15,716 Speaker 2: very well. It clots, it gets infected, it can be problematic. 99 00:06:15,996 --> 00:06:20,156 Speaker 2: So so I became really interested during my training thirty 100 00:06:20,236 --> 00:06:23,956 Speaker 2: years ago in whether or not we could make new 101 00:06:24,116 --> 00:06:27,636 Speaker 2: arteries for patients that would behave like their own veins 102 00:06:27,676 --> 00:06:31,236 Speaker 2: and arteries, but whether we could we could manufacture them, 103 00:06:31,356 --> 00:06:34,636 Speaker 2: you know, make basically spare parts that would be available 104 00:06:34,676 --> 00:06:35,276 Speaker 2: off the shelf. 105 00:06:36,476 --> 00:06:41,316 Speaker 1: How how is that idea received at that time, so. 106 00:06:43,076 --> 00:06:47,556 Speaker 2: People people viewed it as very much like science fiction, 107 00:06:47,836 --> 00:06:53,116 Speaker 2: but also maybe not in a good way. So some 108 00:06:53,356 --> 00:06:55,556 Speaker 2: some of my some of even my close friends, when 109 00:06:55,596 --> 00:06:58,196 Speaker 2: I started working on this, they kind of stepped back 110 00:06:58,236 --> 00:07:02,596 Speaker 2: and looked at me funny, like, are you really serious here? 111 00:07:02,716 --> 00:07:04,236 Speaker 2: Is this something you're really going to try to do? 112 00:07:04,476 --> 00:07:06,396 Speaker 2: You know, grow an artery in a jar? You know, 113 00:07:06,836 --> 00:07:09,836 Speaker 2: nobody will take you seriously if you try to do that. So, yes, 114 00:07:09,956 --> 00:07:12,716 Speaker 2: that was absolutely the vibe in the nineteen nineties. 115 00:07:13,436 --> 00:07:17,756 Speaker 1: So you're a medical resident, your physician, learning you know, 116 00:07:17,876 --> 00:07:19,916 Speaker 1: the clinical skills you need to be a practicing physician. 117 00:07:19,996 --> 00:07:22,196 Speaker 1: Then you get this idea, you want to grow blood 118 00:07:22,236 --> 00:07:28,196 Speaker 1: vessels in a jar. How do you even do that? Like, 119 00:07:28,396 --> 00:07:29,916 Speaker 1: they're not doing that at Mass General. 120 00:07:32,236 --> 00:07:35,236 Speaker 2: Yeah, so the idea of wanting to grow a vessel 121 00:07:35,316 --> 00:07:38,356 Speaker 2: in a jar, You're right, it's not an obvious idea 122 00:07:38,436 --> 00:07:42,116 Speaker 2: that pops into somebody's head. But I was fortunate enough 123 00:07:43,156 --> 00:07:45,796 Speaker 2: to be able to work in the laboratory of Robert Langer, 124 00:07:45,836 --> 00:07:49,596 Speaker 2: who's still a very accomplished investigator, one of the most 125 00:07:49,636 --> 00:07:53,756 Speaker 2: famous investigators at MIT. And as you may know, MIT 126 00:07:53,996 --> 00:07:56,516 Speaker 2: is right across the river from mass General where I 127 00:07:56,676 --> 00:08:00,556 Speaker 2: was doing my residency, and Langer's lab was really one 128 00:08:00,596 --> 00:08:05,756 Speaker 2: of the pioneers in developing this whole concept of tissue engineering, 129 00:08:06,116 --> 00:08:11,316 Speaker 2: basically growing tissues from scratch. So I developed this sort 130 00:08:11,356 --> 00:08:15,516 Speaker 2: of hybrid identity where I would do my clinical training 131 00:08:15,636 --> 00:08:18,276 Speaker 2: during the day at mass General, and then after I 132 00:08:18,476 --> 00:08:21,316 Speaker 2: was done with my cases, I take the subway and 133 00:08:21,676 --> 00:08:24,236 Speaker 2: go across the river and then work in Langer's lab 134 00:08:24,316 --> 00:08:26,476 Speaker 2: in the afternoon and evening and try to figure out 135 00:08:26,676 --> 00:08:29,196 Speaker 2: how you grow an artery and a jar. So I 136 00:08:29,316 --> 00:08:33,836 Speaker 2: got very excited about this and joined his lab in 137 00:08:33,996 --> 00:08:37,356 Speaker 2: ninety five and worked for about three and a half years, 138 00:08:37,916 --> 00:08:41,956 Speaker 2: and then was able to demonstrate and publish really the 139 00:08:42,116 --> 00:08:47,516 Speaker 2: first functional engineered artery in a large animal. We published 140 00:08:47,516 --> 00:08:51,156 Speaker 2: that in nineteen ninety nine, where I took cells from 141 00:08:51,316 --> 00:08:55,316 Speaker 2: pigs and grew arteries for those pigs and then implanted 142 00:08:55,356 --> 00:08:58,596 Speaker 2: them back and they worked, and we published that in 143 00:08:58,676 --> 00:09:01,076 Speaker 2: Science and at the time that made quite a splash. 144 00:09:02,276 --> 00:09:07,156 Speaker 1: So what was the state of tissue engineering more generally 145 00:09:07,316 --> 00:09:10,356 Speaker 1: at that time people do at that time? 146 00:09:11,956 --> 00:09:14,876 Speaker 2: Well, the state of tissue engineering in the nineteen nineties 147 00:09:15,676 --> 00:09:20,156 Speaker 2: was really there had been some successes in what I 148 00:09:20,196 --> 00:09:24,436 Speaker 2: would call sort of simpler connective tissues. So just to 149 00:09:24,476 --> 00:09:28,716 Speaker 2: step back a little bit, our bodies are divided into 150 00:09:28,916 --> 00:09:33,436 Speaker 2: connective tissues and non connective or organ tissues. And connective 151 00:09:33,476 --> 00:09:36,116 Speaker 2: tissues are any tissues that hook one part of the 152 00:09:36,156 --> 00:09:41,836 Speaker 2: body to the other, so that's skin, bone, blood, vessel, tendon, 153 00:09:42,036 --> 00:09:46,076 Speaker 2: what have you. And then organs are obviously heart, liver, kidney, 154 00:09:46,236 --> 00:09:50,116 Speaker 2: stuff like that. So there had been some successes even 155 00:09:50,196 --> 00:09:54,436 Speaker 2: in the nineteen nineties in growing engineered tissues, for example, 156 00:09:54,596 --> 00:09:58,916 Speaker 2: skin and cartilage, and in fact, engineered skin and cartilage 157 00:09:59,156 --> 00:10:01,396 Speaker 2: by the mid to late nineteen nineties were already on 158 00:10:01,516 --> 00:10:07,236 Speaker 2: the market, they were being used in patients, and so 159 00:10:07,996 --> 00:10:11,876 Speaker 2: the early feasibility with some simpler connective tissues had really 160 00:10:11,956 --> 00:10:13,716 Speaker 2: already been demonstrated by that time. 161 00:10:14,476 --> 00:10:17,876 Speaker 1: So, okay, this is whatever twenty five ish years ago. 162 00:10:18,956 --> 00:10:20,996 Speaker 1: Just at the end of last year, at the end 163 00:10:21,036 --> 00:10:25,316 Speaker 1: of twenty twenty three, you applied for FDA approval. You're 164 00:10:25,436 --> 00:10:28,356 Speaker 1: likely to hear back in the next few months. So 165 00:10:28,596 --> 00:10:30,636 Speaker 1: what were a few of the things you had to 166 00:10:30,716 --> 00:10:33,636 Speaker 1: figure out to get from where you were twenty five 167 00:10:33,716 --> 00:10:35,156 Speaker 1: years ago to where you are now. 168 00:10:35,636 --> 00:10:38,956 Speaker 2: So it has been a long journey. Initially we thought, oh, well, 169 00:10:39,076 --> 00:10:42,596 Speaker 2: we'll take a small biopsy from a patient who needs 170 00:10:42,596 --> 00:10:45,036 Speaker 2: an artery and will grow their cells, and then we'll 171 00:10:45,076 --> 00:10:46,996 Speaker 2: make that patient a new artery and then give it 172 00:10:47,116 --> 00:10:47,596 Speaker 2: back to them. 173 00:10:47,796 --> 00:10:49,396 Speaker 1: So it's custom, it's bespoke. 174 00:10:50,036 --> 00:10:54,596 Speaker 2: It was bespoke tissue engineering. The problem with that, though, 175 00:10:54,876 --> 00:10:58,276 Speaker 2: is twofold one. It takes a long time. Yes, so 176 00:10:58,436 --> 00:11:01,316 Speaker 2: if you're a patient with chest pain or. 177 00:11:01,356 --> 00:11:04,356 Speaker 1: Who just got blown up by an IED, or who 178 00:11:04,516 --> 00:11:04,876 Speaker 1: just got. 179 00:11:04,836 --> 00:11:07,196 Speaker 2: Blown up by an IED, you don't really have three 180 00:11:07,276 --> 00:11:09,036 Speaker 2: or four months to wait around for a new art 181 00:11:10,716 --> 00:11:14,036 Speaker 2: So that's fundamentally a problem. But also what we found, 182 00:11:15,116 --> 00:11:17,356 Speaker 2: and this was during some work that I did while 183 00:11:17,356 --> 00:11:20,556 Speaker 2: I was still in academia at Duke University, what we 184 00:11:20,716 --> 00:11:24,836 Speaker 2: found is that for older patients who have vascular disease, 185 00:11:25,716 --> 00:11:28,556 Speaker 2: if we try to take those cells from those patients 186 00:11:28,636 --> 00:11:31,996 Speaker 2: and grow new arteries for those patients, it actually doesn't 187 00:11:32,036 --> 00:11:35,396 Speaker 2: work very well. You know, their vessels are old and 188 00:11:35,516 --> 00:11:40,236 Speaker 2: their cells are old. And we found that and publish that, 189 00:11:40,316 --> 00:11:43,156 Speaker 2: and we have a whole series of papers on that. 190 00:11:43,676 --> 00:11:46,796 Speaker 2: But that really led us to a fundamental pivot, which 191 00:11:46,996 --> 00:11:51,436 Speaker 2: was the insight that we could use young, healthy cells 192 00:11:51,556 --> 00:11:56,716 Speaker 2: from humans, use those to grow arteries. But then after 193 00:11:56,836 --> 00:12:01,276 Speaker 2: we grew the arteries from scratch, we would wash the 194 00:12:01,396 --> 00:12:04,636 Speaker 2: cells out of the engineer tissue. And what that leaves 195 00:12:04,836 --> 00:12:08,996 Speaker 2: behind is extracellular matrix, which can then be implanted into anybody. 196 00:12:09,556 --> 00:12:11,796 Speaker 1: I mean, that's essentially where you arrived and what you 197 00:12:11,916 --> 00:12:15,196 Speaker 1: are doing now, right, And so I want to talk 198 00:12:15,236 --> 00:12:19,396 Speaker 1: about that in a little more detail. Basically, how it works, 199 00:12:19,956 --> 00:12:23,236 Speaker 1: how you make the thing that you make. So where 200 00:12:23,236 --> 00:12:23,676 Speaker 1: do you start. 201 00:12:24,796 --> 00:12:28,956 Speaker 2: So we start with human cells and the cells that 202 00:12:29,716 --> 00:12:33,636 Speaker 2: we use. So right now human site has banks of 203 00:12:33,716 --> 00:12:36,316 Speaker 2: human cells, and in fact, we have enough cells banked 204 00:12:36,876 --> 00:12:40,196 Speaker 2: to support tissue production for the next thirty or forty years. 205 00:12:40,876 --> 00:12:42,836 Speaker 2: We've got a lot of cells. But where those cells 206 00:12:42,916 --> 00:12:47,756 Speaker 2: come from is actually they come from organ and tissue donors. 207 00:12:48,476 --> 00:12:51,916 Speaker 2: So if a patient dies and they become an organ donor, 208 00:12:52,596 --> 00:12:54,916 Speaker 2: their heart might go somewhere and their liver might go 209 00:12:55,036 --> 00:13:00,116 Speaker 2: somewhere else, but there's actually no transplantation use for their 210 00:13:00,156 --> 00:13:05,476 Speaker 2: blood vessels. So we worked with organ procurement organizations and 211 00:13:05,636 --> 00:13:11,076 Speaker 2: we obtained consent from donor families, and we obtained large 212 00:13:11,076 --> 00:13:15,956 Speaker 2: blood vessels aortas from hundreds of different organ donors. We 213 00:13:16,116 --> 00:13:18,596 Speaker 2: isolated cells from those donors, and then we did a 214 00:13:18,716 --> 00:13:24,196 Speaker 2: tremendous amount of screening to identify which cells would really 215 00:13:24,276 --> 00:13:28,676 Speaker 2: be optimal for growing new arteries, and then we established banks. 216 00:13:29,156 --> 00:13:32,956 Speaker 2: So actually we have banks of donor cells now that 217 00:13:33,036 --> 00:13:34,316 Speaker 2: are derived from organ donors. 218 00:13:34,636 --> 00:13:38,556 Speaker 1: So it's like vials of cells in fluid in the 219 00:13:38,636 --> 00:13:40,116 Speaker 1: refrigerator or something like that. 220 00:13:40,396 --> 00:13:44,076 Speaker 2: It's vials of cells stored in liquid nitrogen, so they're 221 00:13:44,156 --> 00:13:47,756 Speaker 2: extremely cold, but that means that the cells can store 222 00:13:47,836 --> 00:13:48,476 Speaker 2: for decades. 223 00:13:49,756 --> 00:13:54,236 Speaker 1: Okay, so very good. That's step one. Get a lot 224 00:13:54,316 --> 00:13:59,156 Speaker 1: of nice, healthy or to cells. And just to be clear, 225 00:13:59,396 --> 00:14:03,356 Speaker 1: by the way, that our blood vessel cells the same 226 00:14:03,476 --> 00:14:05,756 Speaker 1: in all of the vessels. Dumb question, But are the 227 00:14:05,796 --> 00:14:07,676 Speaker 1: cells of the order the same as the cells in 228 00:14:07,836 --> 00:14:08,956 Speaker 1: whatever other blood vessel. 229 00:14:09,716 --> 00:14:14,236 Speaker 2: The cells even within your aorta, there's different flavors of cells, 230 00:14:14,916 --> 00:14:18,276 Speaker 2: and the cells differ between arteries and veins and big 231 00:14:18,396 --> 00:14:21,716 Speaker 2: arteries and small arteries and capillaries. So that was really 232 00:14:21,836 --> 00:14:25,556 Speaker 2: part of the challenge for us, was really identifying which 233 00:14:25,716 --> 00:14:29,316 Speaker 2: subset of cells in the aortas was really the most 234 00:14:31,356 --> 00:14:35,836 Speaker 2: productive for growing new arteries. As it turns out, some 235 00:14:35,996 --> 00:14:37,956 Speaker 2: of the cells in your body, even if you're an 236 00:14:37,956 --> 00:14:42,076 Speaker 2: older person still have this sort of progenitor or stem 237 00:14:42,316 --> 00:14:47,076 Speaker 2: like capability. And those cells we found could grow extensively 238 00:14:47,956 --> 00:14:50,916 Speaker 2: in our process and could grow large numbers of new arteries. 239 00:14:52,396 --> 00:14:55,156 Speaker 1: Great, so you got not only a lot of cells, 240 00:14:55,196 --> 00:14:56,876 Speaker 1: you got a lot of the right kind of cells. 241 00:14:57,396 --> 00:15:00,116 Speaker 2: What do you do with them? Well, when we want 242 00:15:00,196 --> 00:15:02,996 Speaker 2: to grow a batch of arteries. Right now, we grow 243 00:15:03,076 --> 00:15:06,716 Speaker 2: two hundred arteries at a time in a highly automated 244 00:15:06,796 --> 00:15:10,636 Speaker 2: system that we've designed and built over many years. 245 00:15:11,796 --> 00:15:12,676 Speaker 1: Artery factory. 246 00:15:12,836 --> 00:15:16,316 Speaker 2: It's an artery factory, yes, yes, In fact, we have 247 00:15:17,636 --> 00:15:21,196 Speaker 2: eight installed units now. Each unit, which we call a 248 00:15:21,316 --> 00:15:23,996 Speaker 2: Luna two hundred unit, can grow two hundred vessels at 249 00:15:23,996 --> 00:15:24,316 Speaker 2: a time. 250 00:15:24,796 --> 00:15:26,116 Speaker 1: A unit is like a machine. 251 00:15:26,356 --> 00:15:28,676 Speaker 2: It's a machine. It's a machine. It's about as big 252 00:15:28,716 --> 00:15:33,636 Speaker 2: as a school bus, and it's essentially a large incubator 253 00:15:33,836 --> 00:15:38,356 Speaker 2: where we control temperature and humidity and oxygen. But we 254 00:15:38,556 --> 00:15:42,636 Speaker 2: also have inside the school bus, inside the incubator, we 255 00:15:42,836 --> 00:15:48,916 Speaker 2: have bioreactor systems where where we can provide an environment 256 00:15:49,036 --> 00:15:53,996 Speaker 2: for the cells while they're growing, so that the cells 257 00:15:54,236 --> 00:15:56,996 Speaker 2: form new arteries. But I'm sort of jumping ahead a 258 00:15:57,036 --> 00:16:00,316 Speaker 2: little bit. So when we start a batch, what we 259 00:16:00,436 --> 00:16:02,836 Speaker 2: do is we take a tiny vial of cells. It's 260 00:16:02,876 --> 00:16:05,436 Speaker 2: about a fifth of a tea spoon. It's a little 261 00:16:05,476 --> 00:16:08,436 Speaker 2: tiny volume, and we thaw out those cells and then 262 00:16:08,476 --> 00:16:14,396 Speaker 2: we grow them and we let them expand about two thousandfold, 263 00:16:15,516 --> 00:16:18,476 Speaker 2: and then we take we gather all those cells and 264 00:16:18,636 --> 00:16:24,116 Speaker 2: then we essentially walk over to one of our production units, 265 00:16:24,156 --> 00:16:27,276 Speaker 2: one of our Luna two hundreds, and in the Luna 266 00:16:27,316 --> 00:16:31,836 Speaker 2: two hundred is two hundred what we call bioreactor bags. 267 00:16:31,996 --> 00:16:36,356 Speaker 2: Each bag has a has a scaffold inside of it 268 00:16:37,236 --> 00:16:41,076 Speaker 2: that's sterile. And that scaffold is six millimeters in diameter 269 00:16:41,196 --> 00:16:44,276 Speaker 2: and forty centimeters long, So that's the size of the 270 00:16:44,356 --> 00:16:45,076 Speaker 2: artery we grow. 271 00:16:45,236 --> 00:16:48,276 Speaker 1: So and it's made of like plastic or something. 272 00:16:48,436 --> 00:16:52,596 Speaker 2: It's a degradable it's a degradable plastic. It's actually it's 273 00:16:52,716 --> 00:16:56,716 Speaker 2: the same material that's used in degradable sutures. So each 274 00:16:56,836 --> 00:17:00,116 Speaker 2: fiber is about the width of a cell, and there's 275 00:17:00,156 --> 00:17:02,436 Speaker 2: a lot of empty space in between the fibers. But 276 00:17:02,596 --> 00:17:07,116 Speaker 2: this this the shape of the scaffold. We can we 277 00:17:07,196 --> 00:17:10,316 Speaker 2: can shape it into this six millimeter diameter tube that's 278 00:17:10,356 --> 00:17:14,556 Speaker 2: forty centimeters long. And what we do is we take 279 00:17:14,636 --> 00:17:16,956 Speaker 2: the cells that we grow, and we inject them into 280 00:17:16,996 --> 00:17:20,596 Speaker 2: the bag and the cells stick onto the stick, stick 281 00:17:20,636 --> 00:17:23,276 Speaker 2: onto the fibers of the scaffold. It's like a person. 282 00:17:23,396 --> 00:17:26,956 Speaker 2: It's like a person hanging onto a metal pole on 283 00:17:27,116 --> 00:17:29,596 Speaker 2: building scaffolding. If you think of it that, that's kind 284 00:17:29,636 --> 00:17:30,116 Speaker 2: of what it's like. 285 00:17:30,316 --> 00:17:32,716 Speaker 1: And so the cells are grabbing sort of all over 286 00:17:32,876 --> 00:17:35,356 Speaker 1: this little plastic tube, all over the scalfeld. 287 00:17:35,756 --> 00:17:39,476 Speaker 2: Yes, each cell grabs onto a metal pole and they 288 00:17:39,516 --> 00:17:44,756 Speaker 2: hang on for dear life. And then then we basically 289 00:17:45,156 --> 00:17:48,836 Speaker 2: fill the bag, the bioreactor bag, with culture medium. And 290 00:17:49,036 --> 00:17:52,396 Speaker 2: then that culture medium is super secret. It has lots 291 00:17:52,436 --> 00:17:55,036 Speaker 2: of yummy stuff in it that convinces the cells to 292 00:17:55,196 --> 00:18:00,116 Speaker 2: grow and to while they're growing, they secrete proteins like 293 00:18:00,236 --> 00:18:05,716 Speaker 2: collagen and other matrix molecules. What also happens while while 294 00:18:05,756 --> 00:18:08,916 Speaker 2: the cells are growing in the culture medium is we've 295 00:18:08,956 --> 00:18:12,036 Speaker 2: just sign the bioreactor bag so that we can stretch 296 00:18:12,156 --> 00:18:15,716 Speaker 2: the cells as if as if the cells are in 297 00:18:15,836 --> 00:18:18,236 Speaker 2: the wall of an artery and they're feeling your heart beat. 298 00:18:18,676 --> 00:18:22,996 Speaker 1: Huh, because because arteries need to get wider and get 299 00:18:23,076 --> 00:18:26,036 Speaker 1: narrow as the pulse of blood comes in and out. Yes, yes, 300 00:18:26,116 --> 00:18:28,156 Speaker 1: so if you well, there's two different numbers in your 301 00:18:28,196 --> 00:18:29,796 Speaker 1: blood pressure reading exactly. 302 00:18:29,956 --> 00:18:32,236 Speaker 2: There's a there's a higher pressure in a lower pressure. 303 00:18:32,236 --> 00:18:34,116 Speaker 2: And if you put your if you put your finger 304 00:18:34,196 --> 00:18:37,116 Speaker 2: on your wrist, you can feel your pulse. That pulse 305 00:18:37,236 --> 00:18:40,756 Speaker 2: is your artery distending and then and then recoiling every 306 00:18:40,796 --> 00:18:43,436 Speaker 2: time your heart beats. Well, it turns out we learned 307 00:18:43,556 --> 00:18:46,756 Speaker 2: very early. We figured out when I was working in 308 00:18:46,916 --> 00:18:50,116 Speaker 2: Langer's lab in the nineties that if we didn't stretch 309 00:18:50,196 --> 00:18:52,756 Speaker 2: these cells while they were growing, they didn't really make 310 00:18:52,796 --> 00:18:55,116 Speaker 2: an artery because they didn't know they were supposed. 311 00:18:54,756 --> 00:18:57,236 Speaker 1: To do that. So they would be too like rigid, 312 00:18:57,276 --> 00:18:58,116 Speaker 1: they wouldn't be able to. 313 00:18:58,116 --> 00:19:01,756 Speaker 2: They would be pul they would be disorganized. Actually, they 314 00:19:01,796 --> 00:19:04,236 Speaker 2: would just grow randomly because they didn't know what they 315 00:19:04,276 --> 00:19:05,196 Speaker 2: were supposed to be doing. 316 00:19:06,716 --> 00:19:10,076 Speaker 1: Huh. So it's like that that pulse kind of it 317 00:19:10,236 --> 00:19:14,276 Speaker 1: tells them how to grow and organize themselves. That's really interesting. 318 00:19:14,436 --> 00:19:15,436 Speaker 2: It's really interesting. 319 00:19:15,636 --> 00:19:18,916 Speaker 1: Yeah, So so you do that in the bag? How 320 00:19:18,996 --> 00:19:20,596 Speaker 1: do you get them to so you have a little 321 00:19:20,636 --> 00:19:23,476 Speaker 1: sort of imitation heartbeat sort of in the bag. 322 00:19:23,916 --> 00:19:26,996 Speaker 2: We have a little imitation heartbeat in the bag, Yes, 323 00:19:27,796 --> 00:19:30,516 Speaker 2: and every vessel gets stretched the same amount, and they 324 00:19:30,596 --> 00:19:34,316 Speaker 2: get stretched cyclically by this heartbeat for the entire two 325 00:19:34,396 --> 00:19:35,356 Speaker 2: month culture duration. 326 00:19:36,556 --> 00:19:40,876 Speaker 1: So they spend two months growing and learning how to 327 00:19:40,996 --> 00:19:46,716 Speaker 1: be cells in an artery and filling in all the 328 00:19:46,836 --> 00:19:50,196 Speaker 1: spaces on the scaffold on the little plastic tube. What 329 00:19:50,316 --> 00:19:52,636 Speaker 1: happens at the end of that two months, well, at. 330 00:19:52,596 --> 00:19:54,876 Speaker 2: The end of the two months, a couple things have happened. 331 00:19:54,996 --> 00:19:59,516 Speaker 2: One is that that scaffolding, which I said is degradable, 332 00:19:59,796 --> 00:20:02,836 Speaker 2: has mostly degraded, so it's like it's pretty much all gone. 333 00:20:03,436 --> 00:20:06,556 Speaker 2: So what we have by that time is a human 334 00:20:06,716 --> 00:20:11,756 Speaker 2: artery that has these cells and also the collagen matrix 335 00:20:12,196 --> 00:20:15,556 Speaker 2: proteins that they made, and there's really no scaffold left. 336 00:20:16,236 --> 00:20:20,516 Speaker 2: Huh So in a final step, we re drain out 337 00:20:20,556 --> 00:20:23,876 Speaker 2: the culture medium that we use to convince the cells 338 00:20:23,916 --> 00:20:28,996 Speaker 2: to grow, and then we replace it with detergents and 339 00:20:29,276 --> 00:20:33,196 Speaker 2: we basically we spend five days and we washed the 340 00:20:33,316 --> 00:20:34,996 Speaker 2: cells out of the artery. 341 00:20:35,556 --> 00:20:38,676 Speaker 1: Huh So, So after two months, when you take it out, 342 00:20:38,876 --> 00:20:41,956 Speaker 1: it feels like it's a lot like an artery in 343 00:20:42,316 --> 00:20:46,396 Speaker 1: my body, in your body, in anybody's body. But that's 344 00:20:46,476 --> 00:20:48,636 Speaker 1: not good because if you put that in a patient, 345 00:20:48,956 --> 00:20:51,956 Speaker 1: you'll have an immune a bad immune response. That's presumably 346 00:20:52,036 --> 00:20:53,716 Speaker 1: the problem. Why you can't just use that. 347 00:20:54,236 --> 00:20:57,276 Speaker 2: That's the reason, yes, because again these are these are 348 00:20:57,356 --> 00:20:59,396 Speaker 2: cells from a cell bank. So if I if I 349 00:20:59,476 --> 00:21:02,156 Speaker 2: grow that artery and then I implanted in you, your 350 00:21:02,196 --> 00:21:03,796 Speaker 2: body will reject it because. 351 00:21:03,516 --> 00:21:08,396 Speaker 1: It's certainly I'm getting a transplant. And so what is 352 00:21:08,596 --> 00:21:11,636 Speaker 1: what is that final step or that that next step? 353 00:21:12,756 --> 00:21:16,396 Speaker 2: So the final step we call that decellularization. So we 354 00:21:16,676 --> 00:21:20,476 Speaker 2: rinse away the cells, which are really the part that 355 00:21:20,636 --> 00:21:24,236 Speaker 2: creates the immune rejection. But what we leave behind, and 356 00:21:24,316 --> 00:21:28,636 Speaker 2: what we're very careful not to disturb, is the extracellular 357 00:21:28,716 --> 00:21:31,756 Speaker 2: matrix proteins like the collagen that I mentioned, there's actually 358 00:21:32,036 --> 00:21:35,916 Speaker 2: forty or fifty proteins there. The reason that's important is 359 00:21:36,076 --> 00:21:40,716 Speaker 2: because it's really the collagen and the proteins that give 360 00:21:40,796 --> 00:21:45,396 Speaker 2: the vessel all of its mechanical properties. So actually washing 361 00:21:45,556 --> 00:21:48,716 Speaker 2: the cells out of the tissue doesn't change how strong 362 00:21:48,756 --> 00:21:51,836 Speaker 2: it is. It's still just as strong as your arteries. 363 00:21:52,876 --> 00:21:55,116 Speaker 2: After we wash the cells out, the cells are really 364 00:21:55,196 --> 00:21:58,836 Speaker 2: there to be little protein factories, yeah right, but they 365 00:21:58,916 --> 00:22:00,356 Speaker 2: themselves are not very strong. 366 00:22:01,516 --> 00:22:02,116 Speaker 1: Huh So. 367 00:22:02,836 --> 00:22:06,756 Speaker 2: But because collagen is so important, like for example, your 368 00:22:06,836 --> 00:22:10,996 Speaker 2: collagen and my collagen are identical. Huh, they're identical. 369 00:22:11,396 --> 00:22:16,036 Speaker 1: You're saying, there's no kind of there's no potential immune response. 370 00:22:16,076 --> 00:22:18,636 Speaker 1: It's just protein. It's just these exact same protein. You 371 00:22:18,716 --> 00:22:20,836 Speaker 1: couldn't tell the difference, Yes, you couldn't tell who it came. 372 00:22:20,916 --> 00:22:23,516 Speaker 2: Your body, Yes, your body can't tell the difference. And 373 00:22:23,636 --> 00:22:29,876 Speaker 2: so we've implanted these decellularized, engineered arteries into nearly six 374 00:22:29,996 --> 00:22:33,596 Speaker 2: hundred patients over the last eleven years. We've never seen 375 00:22:33,676 --> 00:22:35,516 Speaker 2: a single episode of rejection. 376 00:22:35,916 --> 00:22:38,676 Speaker 1: Because in an immune sense, there's nothing to reject. 377 00:22:39,716 --> 00:22:40,636 Speaker 2: That's what we believe. 378 00:22:40,756 --> 00:22:45,676 Speaker 1: Yes, so now it's like kind of like a dead artery, 379 00:22:45,676 --> 00:22:51,676 Speaker 1: an artery without any personality, a generic artery. You put 380 00:22:51,716 --> 00:22:53,436 Speaker 1: it in a person and a patient. 381 00:22:54,756 --> 00:22:58,276 Speaker 2: What happens then, well, there's a couple things that happened. 382 00:22:58,356 --> 00:23:01,076 Speaker 2: The first thing that happens is that the artery works 383 00:23:01,116 --> 00:23:04,556 Speaker 2: as it should. So the main job of arteries is 384 00:23:04,636 --> 00:23:07,196 Speaker 2: to conduct blood flow so that you can get blood 385 00:23:07,236 --> 00:23:10,436 Speaker 2: from point A to point B. So that happens as 386 00:23:10,476 --> 00:23:12,396 Speaker 2: soon as the surgeon sews it in and takes the 387 00:23:12,476 --> 00:23:15,956 Speaker 2: clamps off. So some people worry, g we wash the 388 00:23:16,076 --> 00:23:16,996 Speaker 2: cells out, will. 389 00:23:16,916 --> 00:23:17,716 Speaker 1: It be leaky. 390 00:23:19,596 --> 00:23:24,956 Speaker 2: That doesn't happen. We don't see that. But what's probably 391 00:23:25,116 --> 00:23:29,796 Speaker 2: cooler is that over time, sells from the patient see 392 00:23:29,916 --> 00:23:34,436 Speaker 2: this naked artery and to them it sort of looks 393 00:23:34,516 --> 00:23:39,476 Speaker 2: like an empty apartment building. And what we've seen happen, 394 00:23:39,556 --> 00:23:42,956 Speaker 2: in fact we've published this, is that cells from the 395 00:23:43,076 --> 00:23:50,596 Speaker 2: patient migrate into the acellular artery and they start off 396 00:23:50,676 --> 00:23:54,156 Speaker 2: being progenitor cells, but they become vascular cells. So over 397 00:23:54,236 --> 00:23:58,636 Speaker 2: a period of months, this non living thing becomes a 398 00:23:58,796 --> 00:24:03,596 Speaker 2: living artery and it's the patient's own. So this is really, 399 00:24:03,796 --> 00:24:07,476 Speaker 2: I think this is regenerative medicine in the truest sense. 400 00:24:09,836 --> 00:24:13,396 Speaker 1: Can you tell the difference whatever a year later, between 401 00:24:13,476 --> 00:24:16,116 Speaker 1: the section of artery that you put in and the 402 00:24:16,196 --> 00:24:17,076 Speaker 1: patient's own artery. 403 00:24:18,196 --> 00:24:22,076 Speaker 2: You can tell differences. There are still subtle differences. There 404 00:24:22,196 --> 00:24:25,956 Speaker 2: is one there's one stretchy protein called elastin, which is 405 00:24:25,996 --> 00:24:29,956 Speaker 2: in all of our arteries, but are the engineered arteries 406 00:24:29,996 --> 00:24:32,996 Speaker 2: don't have elastin, So that's actually the easiest way to tell. 407 00:24:34,076 --> 00:24:36,796 Speaker 2: Aside from that, there's not a lot of differences. 408 00:24:38,036 --> 00:24:40,596 Speaker 1: Does the absence of elastin make a functional difference? 409 00:24:41,756 --> 00:24:45,076 Speaker 2: It doesn't seem to. This is something that I used 410 00:24:45,076 --> 00:24:48,476 Speaker 2: to worry about as a younger professor ten, fifteen, twenty 411 00:24:48,596 --> 00:24:53,476 Speaker 2: years ago, but over a thousand patient years of exposure 412 00:24:53,556 --> 00:24:55,196 Speaker 2: tells us that it probably doesn't matter. 413 00:24:56,196 --> 00:24:59,516 Speaker 1: It's weird that there's a thing in our arteries that 414 00:24:59,596 --> 00:25:01,956 Speaker 1: we could do without. You'd think that, would you know? 415 00:25:03,116 --> 00:25:04,996 Speaker 1: I like the way you know fish that live in 416 00:25:05,076 --> 00:25:07,316 Speaker 1: caves for a million years don't have eyes anymore because 417 00:25:07,316 --> 00:25:09,036 Speaker 1: it's costly to have eyes, and if you don't need 418 00:25:09,156 --> 00:25:10,036 Speaker 1: they evolve away. 419 00:25:10,836 --> 00:25:14,876 Speaker 2: Well, I think that's the difference between having no elastin 420 00:25:15,116 --> 00:25:18,436 Speaker 2: in your body, but having or not having elastin just 421 00:25:18,516 --> 00:25:21,356 Speaker 2: in a short segment. So if you have no elastin 422 00:25:21,436 --> 00:25:24,436 Speaker 2: in your whole body, that's actually that makes life very 423 00:25:24,556 --> 00:25:27,476 Speaker 2: very hard for your heart. However, if it's just a 424 00:25:27,596 --> 00:25:30,796 Speaker 2: short segment of the vessels in your body that don't 425 00:25:30,836 --> 00:25:33,076 Speaker 2: have elastin, your heart doesn't care too much. 426 00:25:36,636 --> 00:25:52,636 Speaker 1: We'll be back in a minute. Laura's company, Humocite, applied 427 00:25:52,916 --> 00:25:55,836 Speaker 1: late last year for FDA approval. They expect to hear 428 00:25:55,916 --> 00:25:59,196 Speaker 1: back this summer, and she told me about the evidence 429 00:25:59,436 --> 00:26:02,076 Speaker 1: that made her think that made the company think that 430 00:26:02,196 --> 00:26:05,916 Speaker 1: they were finally ready to apply for FDA approval. For 431 00:26:06,076 --> 00:26:08,876 Speaker 1: widespread use of these vessels they're creating. 432 00:26:09,796 --> 00:26:13,876 Speaker 2: So the trial that is supporting our current application at 433 00:26:13,916 --> 00:26:17,876 Speaker 2: the FDA was conducted at nineteen trauma centers in the 434 00:26:18,036 --> 00:26:21,716 Speaker 2: US and Israel, and we treated a total of seventy 435 00:26:21,836 --> 00:26:27,556 Speaker 2: patients who had all sorts of injuries, you know, car accidents, 436 00:26:27,796 --> 00:26:32,116 Speaker 2: gunshot wounds, industrial accidents. We treated a guy who worked 437 00:26:32,156 --> 00:26:34,916 Speaker 2: on a farm who was crushed by a cow, We 438 00:26:35,036 --> 00:26:37,316 Speaker 2: treated a woman who was crushed by a crane on 439 00:26:37,436 --> 00:26:40,636 Speaker 2: a dock. I mean, just all sorts of terrible injuries. 440 00:26:41,076 --> 00:26:43,956 Speaker 2: And then we followed those patients, many of them were 441 00:26:43,996 --> 00:26:47,356 Speaker 2: still following, But it was really the data from that 442 00:26:47,636 --> 00:26:53,876 Speaker 2: pivotal trial that showed really excellent outcomes in terms of safety, 443 00:26:53,996 --> 00:26:56,956 Speaker 2: but also in terms of how well blood flow was 444 00:26:57,036 --> 00:27:01,156 Speaker 2: restored and a very low number of amputations and infections. 445 00:27:01,876 --> 00:27:05,556 Speaker 2: So seeing all of that clinical data together from this 446 00:27:05,716 --> 00:27:09,556 Speaker 2: pivotal trial and then combined with the Ukraine exit experience, 447 00:27:09,636 --> 00:27:13,476 Speaker 2: because the Ukraine humanitarian effort was ongoing at the same 448 00:27:13,556 --> 00:27:16,756 Speaker 2: time we were doing this pivotal trial, So putting all 449 00:27:16,836 --> 00:27:20,676 Speaker 2: of that information together is what really formed the basis 450 00:27:20,796 --> 00:27:22,716 Speaker 2: of our filing with the FDA. Last year. 451 00:27:23,756 --> 00:27:29,516 Speaker 1: You mentioned that there are other options. Where do your 452 00:27:29,596 --> 00:27:33,636 Speaker 1: arteries fit in this sort of you know, comparative landscape, 453 00:27:34,036 --> 00:27:35,916 Speaker 1: like when is something else better? And when is one 454 00:27:35,956 --> 00:27:36,796 Speaker 1: of your arteries better? 455 00:27:37,276 --> 00:27:40,236 Speaker 2: Well, this is something that you know the FDA would 456 00:27:40,316 --> 00:27:44,236 Speaker 2: argue is probably their decision to make. Our argument is 457 00:27:44,356 --> 00:27:48,516 Speaker 2: that in patients who don't have their own vein available, 458 00:27:49,316 --> 00:27:52,396 Speaker 2: and for injured patients, it may be because their limbs 459 00:27:52,436 --> 00:27:56,476 Speaker 2: are injured. It may be because the need to restore 460 00:27:56,556 --> 00:28:00,196 Speaker 2: blood flow is so acute that the surgeons don't don't 461 00:28:00,236 --> 00:28:02,796 Speaker 2: have that extra hour to harvest the vein. It could 462 00:28:02,876 --> 00:28:05,276 Speaker 2: be that the surgeon doesn't want to injure the patient. 463 00:28:05,356 --> 00:28:09,036 Speaker 2: Further so, in patients in whom vein is not feed 464 00:28:12,156 --> 00:28:15,796 Speaker 2: our argument is that the hav is an excellent option. 465 00:28:16,076 --> 00:28:20,636 Speaker 2: And our data showed when we compared our outcomes to 466 00:28:21,596 --> 00:28:26,596 Speaker 2: outcomes of patients who are treated with plastic graphs like 467 00:28:26,676 --> 00:28:30,836 Speaker 2: made out of teflon in trauma, our data showed that 468 00:28:30,916 --> 00:28:34,756 Speaker 2: our outcomes are substantially better than plastic graphs. 469 00:28:35,836 --> 00:28:38,836 Speaker 1: What are some of the next things that you're working on, 470 00:28:38,956 --> 00:28:40,436 Speaker 1: Like what are you trying to figure out now? 471 00:28:41,996 --> 00:28:45,236 Speaker 2: Well, on the clinical side, we have trials that are 472 00:28:45,316 --> 00:28:48,996 Speaker 2: under ways that we're still collecting data on in patients 473 00:28:49,076 --> 00:28:55,636 Speaker 2: with kidney failure who we're studying our engineered vessels as 474 00:28:56,956 --> 00:29:00,476 Speaker 2: what we call a dialysis access, which is where our 475 00:29:00,596 --> 00:29:03,436 Speaker 2: vessels are sown into the patient's arm between an artery 476 00:29:03,476 --> 00:29:07,116 Speaker 2: and a vein, and then that vessel is used in 477 00:29:07,236 --> 00:29:11,676 Speaker 2: the dialysis clinic where nurses poke needles into the vessel 478 00:29:11,756 --> 00:29:14,916 Speaker 2: and use that so the patient can get dialysis. So 479 00:29:16,156 --> 00:29:19,756 Speaker 2: we're studying that indication, and in fact, we have another 480 00:29:19,876 --> 00:29:22,716 Speaker 2: pivotal trial that we expect to read out in the 481 00:29:22,796 --> 00:29:25,916 Speaker 2: third quarter of this year in twenty twenty four that 482 00:29:26,036 --> 00:29:30,756 Speaker 2: will tell us if the HAV works better in dialysis 483 00:29:31,116 --> 00:29:35,156 Speaker 2: then basically the gold standard, which is where a surgeon 484 00:29:35,316 --> 00:29:37,516 Speaker 2: sows an artery in a vein together directly. 485 00:29:38,196 --> 00:29:41,316 Speaker 1: So that's the kind of short term future. It's basically 486 00:29:41,396 --> 00:29:47,316 Speaker 1: trying to trying to get the dialysis related indication. When 487 00:29:47,316 --> 00:29:50,396 Speaker 1: you think more long term, if you think, I don't 488 00:29:50,396 --> 00:29:51,916 Speaker 1: even know how many years that is for you, Is 489 00:29:51,956 --> 00:29:53,356 Speaker 1: it five years, is it ten years? 490 00:29:53,436 --> 00:29:53,476 Speaker 2: Like? 491 00:29:53,556 --> 00:29:54,316 Speaker 1: What do you think about? 492 00:29:55,396 --> 00:29:58,196 Speaker 2: So for the last several years, we've been making smaller 493 00:29:58,316 --> 00:30:02,716 Speaker 2: diameter vessels that are the right size for hard bypass, 494 00:30:04,676 --> 00:30:07,276 Speaker 2: and we've actually been testing these three and a half 495 00:30:07,396 --> 00:30:13,556 Speaker 2: millimeter vessels doing heart bypasses in primates, non human primates, 496 00:30:13,636 --> 00:30:17,796 Speaker 2: and other large animals. And we're collecting a long term 497 00:30:17,916 --> 00:30:21,676 Speaker 2: data to submit as a file to the FDA in 498 00:30:21,876 --> 00:30:24,836 Speaker 2: order to gain approval to do a phase one trial 499 00:30:24,916 --> 00:30:27,596 Speaker 2: in patients who need a heart bypass but who don't 500 00:30:27,636 --> 00:30:31,436 Speaker 2: have their own vein to do the bypass. So we 501 00:30:31,516 --> 00:30:35,316 Speaker 2: would hope to start that first in human trial in 502 00:30:35,436 --> 00:30:37,476 Speaker 2: heart bypass in the next couple of years. 503 00:30:38,476 --> 00:30:45,276 Speaker 1: So bypass is a unfortunately wildly common procedure. My dad 504 00:30:45,356 --> 00:30:49,556 Speaker 1: had one, my grandfather had a few, taking statins and 505 00:30:49,636 --> 00:30:52,076 Speaker 1: running all the time and hopes that I'll dodge that bullet. 506 00:30:52,116 --> 00:30:56,196 Speaker 1: But who knows. So presumably that would be a very 507 00:30:56,276 --> 00:30:58,676 Speaker 1: large market. I mean, it's also the case that many 508 00:30:58,796 --> 00:31:02,556 Speaker 1: patients are able to use their own veins. You mentioned 509 00:31:02,676 --> 00:31:05,796 Speaker 1: you're thinking about patients who can't in what instances are 510 00:31:05,876 --> 00:31:08,996 Speaker 1: graphs unavailable for patients getting bypassed and what do doctors 511 00:31:09,236 --> 00:31:10,116 Speaker 1: now in those instances. 512 00:31:11,796 --> 00:31:15,236 Speaker 2: Well, there's lots of situations where patients who need a 513 00:31:15,356 --> 00:31:18,036 Speaker 2: vein for hard bypass don't have it. So, for example, 514 00:31:18,236 --> 00:31:21,436 Speaker 2: if you have varicose veins, if your veins are very dilated. 515 00:31:22,036 --> 00:31:27,116 Speaker 2: Surgeons can't use them in the modern area era vein 516 00:31:27,276 --> 00:31:32,116 Speaker 2: clinics are sclerosing people's veins all the time so that 517 00:31:32,836 --> 00:31:35,996 Speaker 2: ladies can have beautiful legs at the beach, which is 518 00:31:36,116 --> 00:31:37,956 Speaker 2: great in the short term, but not so good in 519 00:31:37,996 --> 00:31:42,236 Speaker 2: the long term. And then lastly, as we know, there's 520 00:31:42,316 --> 00:31:46,476 Speaker 2: a growing obesity and diabetes epidemic in the United States 521 00:31:46,556 --> 00:31:49,956 Speaker 2: most of the western world. For those patients, if you 522 00:31:50,076 --> 00:31:52,756 Speaker 2: cut into their legs and take their vein out, they 523 00:31:52,836 --> 00:31:56,356 Speaker 2: have a higher rate of complications. Their incisions don't heal, 524 00:31:56,436 --> 00:31:59,796 Speaker 2: they get infected, they have all sorts of problems. 525 00:31:59,996 --> 00:32:03,556 Speaker 1: Are there not teflon artificial veins that can be used 526 00:32:03,596 --> 00:32:04,316 Speaker 1: for bypass? 527 00:32:05,676 --> 00:32:10,356 Speaker 2: There's nothing artificial that works for those small diameter vessels 528 00:32:10,396 --> 00:32:16,236 Speaker 2: in your heart, despite a huge need, there simply isn't anything. 529 00:32:17,196 --> 00:32:19,116 Speaker 1: So you said that when you started out, you know, 530 00:32:19,236 --> 00:32:23,356 Speaker 1: twenty five thirty years ago, making connective tissue like blood vessels, 531 00:32:23,436 --> 00:32:27,356 Speaker 1: like what you're doing, seemed much easier than making solid organs. 532 00:32:27,756 --> 00:32:29,836 Speaker 1: And so I'm curious, after all this time and all 533 00:32:29,876 --> 00:32:33,556 Speaker 1: the advancements there have been, does making a solid organ 534 00:32:33,676 --> 00:32:38,396 Speaker 1: in a lab still feel you know, wild hard it's. 535 00:32:38,876 --> 00:32:43,476 Speaker 2: Still wild, hard, but it's starting to feel tractable. So 536 00:32:44,116 --> 00:32:46,396 Speaker 2: one of the parts that we haven't talked about is, 537 00:32:46,596 --> 00:32:49,116 Speaker 2: you know, I've had this dual life for many years 538 00:32:49,236 --> 00:32:51,836 Speaker 2: as a Right now I'm the CEO of Humusite, and 539 00:32:51,876 --> 00:32:55,356 Speaker 2: I'm not an academic anymore. But for many years I 540 00:32:55,476 --> 00:32:57,796 Speaker 2: sort of had one foot in academia and one foot 541 00:32:57,836 --> 00:33:01,756 Speaker 2: in my company. And while I was working as a 542 00:33:01,796 --> 00:33:06,236 Speaker 2: professor at Yale, we were the first lab to actually 543 00:33:06,396 --> 00:33:11,316 Speaker 2: be able to grow engineered lung and implant them in 544 00:33:11,476 --> 00:33:13,956 Speaker 2: rats and showed that they could exchange gas for a 545 00:33:14,036 --> 00:33:19,676 Speaker 2: few hours. So we have a pathway I believe to 546 00:33:19,996 --> 00:33:24,196 Speaker 2: growing more complex tissues, lungs in particular, And in fact, 547 00:33:24,276 --> 00:33:27,836 Speaker 2: some of my former trainees from my labors are off 548 00:33:27,956 --> 00:33:31,476 Speaker 2: scattered at different institutions working on that problem. 549 00:33:31,236 --> 00:33:36,236 Speaker 1: Right now on lab grown lungs. In lab grown lungs 550 00:33:36,796 --> 00:33:41,716 Speaker 1: are lungs less complex than other organs? Is that why lungs? 551 00:33:43,036 --> 00:33:48,996 Speaker 2: Lungs are not less complex, but lungs, Interestingly, they're the 552 00:33:49,116 --> 00:33:53,476 Speaker 2: only organ in your body that's mostly empty space. And 553 00:33:54,156 --> 00:33:58,596 Speaker 2: in biology, in biotechnology, we're very good at growing thin 554 00:33:58,756 --> 00:34:02,916 Speaker 2: layers of cells or monolayers or thin collections of cells. 555 00:34:03,396 --> 00:34:06,036 Speaker 2: One of the things that we did figure out in 556 00:34:06,236 --> 00:34:10,716 Speaker 2: my academic lab is that instead of using a plastic 557 00:34:10,796 --> 00:34:16,356 Speaker 2: scaffold for lungs, what we can probably do is take 558 00:34:16,596 --> 00:34:19,636 Speaker 2: a native lung, either a human lung or maybe a 559 00:34:19,676 --> 00:34:24,116 Speaker 2: primate lung or a pig lung and decellularize that lung 560 00:34:24,996 --> 00:34:28,596 Speaker 2: and use that as a scaffold. In that case, we 561 00:34:28,716 --> 00:34:33,476 Speaker 2: could maybe take stem cells from the patient and repopulate 562 00:34:33,796 --> 00:34:36,596 Speaker 2: that scaffold that has all of the structure of the lung, 563 00:34:36,716 --> 00:34:39,196 Speaker 2: all the air sacs, all the blood vessels, all of 564 00:34:39,316 --> 00:34:44,436 Speaker 2: that important lung structure. If we can repopulate that with cells, 565 00:34:44,476 --> 00:34:47,516 Speaker 2: then we're basically we kind of have a leg up. 566 00:34:47,836 --> 00:34:50,156 Speaker 2: We've got the lung structure to start with, and then 567 00:34:50,236 --> 00:34:52,716 Speaker 2: we just repopulate it with cells from the patient, and 568 00:34:52,796 --> 00:34:55,076 Speaker 2: then we've got a designer organ. 569 00:34:59,276 --> 00:35:01,356 Speaker 1: We'll be back in a minute with the Lightning Round. 570 00:35:12,876 --> 00:35:15,076 Speaker 1: So I'm cognizant of the time. I just want to 571 00:35:15,436 --> 00:35:20,156 Speaker 1: ask you some Lightning Round questions to finish. 572 00:35:21,836 --> 00:35:21,876 Speaker 2: That. 573 00:35:22,156 --> 00:35:25,556 Speaker 1: They will be slightly more random than the questions I've 574 00:35:25,556 --> 00:35:30,276 Speaker 1: asked you so far. What's one thing you learned from 575 00:35:30,316 --> 00:35:30,916 Speaker 1: Bob Langer. 576 00:35:33,716 --> 00:35:37,236 Speaker 2: I learned from Bob Langer that time is the one 577 00:35:37,316 --> 00:35:44,116 Speaker 2: thing you can't get back that things cost. Getting things 578 00:35:44,156 --> 00:35:47,356 Speaker 2: done cost effort, and they cost money, and they cost time. 579 00:35:49,116 --> 00:35:51,676 Speaker 2: You can get more effort, and you can get more money, 580 00:35:52,036 --> 00:35:55,916 Speaker 2: but you can't get more time. So he was always 581 00:35:55,996 --> 00:35:59,076 Speaker 2: focused on finding the most efficient way to get something 582 00:35:59,196 --> 00:36:03,316 Speaker 2: done that took the least amount of time, because, as 583 00:36:03,396 --> 00:36:06,756 Speaker 2: it turns out, everything takes longer than you think it's gonna. 584 00:36:08,916 --> 00:36:11,556 Speaker 1: It's interesting to think about him that way, right because 585 00:36:11,556 --> 00:36:13,236 Speaker 1: I interviewed him and I was like, how did you 586 00:36:13,356 --> 00:36:16,556 Speaker 1: do so many things? And he I don't know if 587 00:36:16,596 --> 00:36:19,396 Speaker 1: he knew, but like that answer that you just gave 588 00:36:19,676 --> 00:36:21,676 Speaker 1: is a pretty good answer for how he did so 589 00:36:21,796 --> 00:36:27,396 Speaker 1: many things. So it was what the mid nineties is 590 00:36:27,436 --> 00:36:31,716 Speaker 1: that right when you started sort of getting into regenerative medicine, 591 00:36:32,516 --> 00:36:36,596 Speaker 1: And I'm curious, you know, that's thirty years ago now, 592 00:36:38,196 --> 00:36:42,916 Speaker 1: and I'm curious looking back now, it's sort of what 593 00:36:43,116 --> 00:36:46,756 Speaker 1: you thought then. What is something that's progressed more quickly 594 00:36:47,196 --> 00:36:48,076 Speaker 1: than you thought it would? 595 00:36:49,556 --> 00:36:57,356 Speaker 2: Tools tools one of the reasons that sell therapy and 596 00:36:57,476 --> 00:37:01,116 Speaker 2: regenerative medicine is taking off now and we'll continue to 597 00:37:01,316 --> 00:37:06,396 Speaker 2: just explode in the next couple decades is tools. We 598 00:37:06,476 --> 00:37:09,996 Speaker 2: can look at a tissue that we're growing and sort 599 00:37:10,036 --> 00:37:17,036 Speaker 2: of gate generate sort of a report card of here's 600 00:37:17,036 --> 00:37:19,596 Speaker 2: how the cells are behaving. You know, fifteen percent of 601 00:37:19,636 --> 00:37:21,916 Speaker 2: the cells are behaving correctly, eighty five percent of the 602 00:37:21,996 --> 00:37:24,516 Speaker 2: cells are not doing what they're supposed to do. And 603 00:37:24,636 --> 00:37:27,036 Speaker 2: I can compare that report card to what a native 604 00:37:27,076 --> 00:37:29,316 Speaker 2: tissue looks like, and then I can go back and 605 00:37:29,476 --> 00:37:31,756 Speaker 2: fix what I'm doing on the engineered side and just 606 00:37:31,876 --> 00:37:34,596 Speaker 2: iterate that way, it allows you to make a roadmap. 607 00:37:35,956 --> 00:37:38,196 Speaker 1: What's something that has progressed more slowly than you would 608 00:37:38,236 --> 00:37:38,516 Speaker 1: have thought. 609 00:37:40,516 --> 00:37:47,916 Speaker 2: I think that. I think that the development of functional 610 00:37:48,036 --> 00:37:51,676 Speaker 2: connective tissues has progressed more slowly than I would have thought. 611 00:37:52,836 --> 00:37:55,996 Speaker 2: The thing you do, the thing I do, the thing 612 00:37:56,076 --> 00:38:01,516 Speaker 2: I do, and I'm surprised at that if we look 613 00:38:01,556 --> 00:38:03,876 Speaker 2: at so as I said, in the nineteen nineties, there 614 00:38:03,916 --> 00:38:08,556 Speaker 2: were approved versions of tissue engineered cartilage and tissue engineered 615 00:38:08,596 --> 00:38:11,916 Speaker 2: skin that were on the market in the US or Europe. 616 00:38:11,996 --> 00:38:14,116 Speaker 1: Did those just turn out to be way easier than 617 00:38:14,156 --> 00:38:14,716 Speaker 1: everything else? 618 00:38:15,076 --> 00:38:19,196 Speaker 2: Or what they are? They're easier, the tissues are simpler, 619 00:38:19,916 --> 00:38:23,996 Speaker 2: and the what we would say to our design requirements 620 00:38:24,276 --> 00:38:28,516 Speaker 2: are a little bit less stringent. So what has progressed 621 00:38:28,556 --> 00:38:31,596 Speaker 2: more slowly than I would have thought is making tissues 622 00:38:31,716 --> 00:38:36,676 Speaker 2: that have tougher design criteria and doing that successfully. 623 00:38:38,076 --> 00:38:41,196 Speaker 1: Seems like you're almost there, We're. 624 00:38:41,116 --> 00:38:43,876 Speaker 2: Almost there, But it does I've been working on it 625 00:38:43,956 --> 00:38:45,316 Speaker 2: for thirty years. It does take time. 626 00:38:45,796 --> 00:38:48,796 Speaker 1: Did you feel like you were almost there ten years ago. 627 00:38:49,356 --> 00:38:51,436 Speaker 2: I felt like I was almost there twenty years ago. 628 00:38:54,716 --> 00:38:55,876 Speaker 1: But this time you mean it? 629 00:38:56,916 --> 00:39:00,996 Speaker 2: This time, I mean it? But no, I think you know. 630 00:39:01,236 --> 00:39:04,876 Speaker 2: I think it's to make tissues, you have to understand 631 00:39:04,956 --> 00:39:08,556 Speaker 2: the cell biology and that single cell information that I mentioned, 632 00:39:09,276 --> 00:39:11,676 Speaker 2: But you also really have to come to grips with 633 00:39:12,396 --> 00:39:16,076 Speaker 2: what the tissue does and what characteristics the whole tissue 634 00:39:16,196 --> 00:39:20,596 Speaker 2: must have in order to function. And that's a complicated 635 00:39:20,676 --> 00:39:23,476 Speaker 2: set of problems, and it takes it. You know, one 636 00:39:23,556 --> 00:39:25,956 Speaker 2: person can't do it all. It takes a really terrific 637 00:39:26,036 --> 00:39:27,636 Speaker 2: team working on it for a long time. 638 00:39:28,276 --> 00:39:30,796 Speaker 1: Do you think that having a founding team that was 639 00:39:30,876 --> 00:39:33,276 Speaker 1: all women affected the culture of the company. 640 00:39:34,876 --> 00:39:37,116 Speaker 2: It affected a lot of things. It affected the culture 641 00:39:37,116 --> 00:39:44,036 Speaker 2: of the company. Humo site has never suffered from a 642 00:39:44,196 --> 00:39:48,636 Speaker 2: sense that women can't be heard in a meeting. It's 643 00:39:48,676 --> 00:39:52,876 Speaker 2: actually allowed us to attract and retain incredibly smart and 644 00:39:52,996 --> 00:39:55,436 Speaker 2: high powered women because they know they will never have 645 00:39:55,556 --> 00:39:58,516 Speaker 2: to fight that uphill battle. So it actually gives us 646 00:39:58,556 --> 00:40:03,516 Speaker 2: an edge in terms of recruitment. But in retrospect, now 647 00:40:03,636 --> 00:40:06,636 Speaker 2: having been at this for nearly twenty years, I would 648 00:40:06,676 --> 00:40:09,596 Speaker 2: say that in the early years, I think it made 649 00:40:09,596 --> 00:40:13,476 Speaker 2: it harder for us to raise money. People write about this, 650 00:40:13,876 --> 00:40:16,996 Speaker 2: and people used to ask me about it early on, 651 00:40:17,196 --> 00:40:21,996 Speaker 2: and I sort of discarded it as being paranoid. But 652 00:40:22,156 --> 00:40:26,036 Speaker 2: now looking back, I think it hurt us. I just 653 00:40:26,156 --> 00:40:29,956 Speaker 2: think that people there's an expectation that, well, if this 654 00:40:30,116 --> 00:40:32,516 Speaker 2: is an all woman company, then you know, maybe this 655 00:40:32,676 --> 00:40:33,396 Speaker 2: isn't going to work. 656 00:40:34,356 --> 00:40:37,316 Speaker 1: What's one thing you wish more people understood about cells? 657 00:40:40,396 --> 00:40:46,116 Speaker 2: I wish that people appreciated how smart cells are. What 658 00:40:46,196 --> 00:40:51,276 Speaker 2: do you mean, Well, what I've learned is that if 659 00:40:51,356 --> 00:40:56,116 Speaker 2: I work with the right starting cells, if I give 660 00:40:56,196 --> 00:41:01,676 Speaker 2: them about eight cues, not one que, but it's not 661 00:41:01,796 --> 00:41:04,596 Speaker 2: a thousand ques. If I give them about eight cues, 662 00:41:05,716 --> 00:41:08,596 Speaker 2: a couple of the right growth factors, right amount of stretch, 663 00:41:10,396 --> 00:41:13,556 Speaker 2: you know, right temperature, right oxygen level. If I give 664 00:41:13,556 --> 00:41:16,756 Speaker 2: them about eight cues, they take it and run with it, 665 00:41:17,556 --> 00:41:21,516 Speaker 2: and without any supervision for me, they make a brand 666 00:41:21,596 --> 00:41:24,116 Speaker 2: new artery that looks and feels like the real thing. 667 00:41:25,276 --> 00:41:29,276 Speaker 2: And that's a remarkable amount of intelligence inside a little 668 00:41:29,316 --> 00:41:33,596 Speaker 2: tiny cell. So our cells are very self directed, they're 669 00:41:33,716 --> 00:41:37,116 Speaker 2: very smart, and in order to coax them to make 670 00:41:37,716 --> 00:41:40,116 Speaker 2: spare parts, we just have to figure out what that 671 00:41:40,316 --> 00:41:41,876 Speaker 2: right handful of cues is. 672 00:41:46,756 --> 00:41:49,916 Speaker 1: Laura Nicholson is the co founder and CEO of Humo site. 673 00:41:50,996 --> 00:41:54,196 Speaker 1: Today's show was produced by Gabriel Hunter Chang. It was 674 00:41:54,556 --> 00:41:57,996 Speaker 1: edited by Lydia jene Kott and engineered by Sarah Bruguer. 675 00:41:58,476 --> 00:42:01,556 Speaker 1: You can email us at problem at Pushkin dot FM. 676 00:42:02,196 --> 00:42:04,476 Speaker 1: I'm Jacob Goldstein and we'll be back next week with 677 00:42:04,596 --> 00:42:11,876 Speaker 1: another episode of What's Your Problem That's True sn