Kim Solez Tissue Engineering Pathology Meets Human Cell Atlas A Glimpse into the Future of Pathology

Kim Solez Tissue Engineering Pathology Meets Human Cell Atlas A Glimpse into the Future of Pathology

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I talk. About cooperation, with, a human, cell Atlas. Project. And. This. Is an unusual area. Of science. Most. Areas, of science, if you want to hear about them you go to the standard, meetings, and they decide, what, things get on the program and so the most important, stuff gets a lot, of play on the program. You can tell just from looking at, the meeting program. What areas you should be learning about, the. Big meetings, that, I go, to have been entirely, silent. About the human cell Atlas. Project. Even, though it's. Probably going to be as large or larger than. The. Human, genome. Project. And. Of similar. Importance. Well how did I find out I found, out about it on, Facebook. And on Facebook, LinkedIn, you know social, media it's just all, over, the, place you can't be on Facebook, and not have heard of the human, cell, Atlas, but if you're, one of these physicians. Or scientists, who are frightened, to death. Facebook. You know buddy completely. You. Know blindsided. By. This there'll, be big things happening, with a human, cell. Atlas the single-cell. Genomics. Using. Microfluidics. To, kind of analyze. Genomics. Of cells one by one. That. If you just take the old traditional, ways of keeping up with science, you'll know nothing, about it if you're, big on social media, you'll know everything about it so, it makes it hard for me to tell you how important. It really is, I, would say it I can't, really judge that, but it is related, to. Tissue. Engineering, pathology. Because people, say to me well can't, you kind of summarize, like. One sentence, or phrase what. Tissue engineering, pathology. Is, and. It. Is getting, the right cells, and the right places and a bioengineered. Organ. Well. That sounds, simple if. You think you know hot cells, are supposed to, be there but, as you'll find out in this lecture. We thought that we knew. That like for the past eighteen or, you, know 20 years we. Thought, we. Knew in every organ, in the human body how, many cell types there were and exactly what they were and so on and. Now that you can analyze. The. Genome, of individual, cells one by one it turns out they're a lot more, cell types. Than, we ever thought so, that's. The. Way that the two are related. So. Regenerative. Medicine. Tissue engineering cell. Therapy, there. Are three terms used, for, similar, things. Regenerative. Medicine. Over the past, 20. Years or so the. Use of the term has remained, more or less constant. Cell. Therapy, has been going up. Tissue. Engineering, has been going down but. They they don't quite mean, exactly. The same thing but they, they're they're use in sort of, overlapping. Ways. And. They. Have to do not only with like generating. Organs, from. Scratch, from. Stem. Cells like. Recreating. Embryological. Development. But. Also taking. A, previous. Organ. Flushing. Out all the, cell's so you have, sort, of the the. Framework. That the cells were, we're, in and then. Reinforcing. Stem. Cells into. That. Template. And then. Growing, a new, organ that way it also has to do with repair, of existing, organs. So. Take an organ that has. Damaged. And fuse, stem. Cells in it into. It that will repair. The organ so although things. Are. Regenerative. Medicine, tissue, engineering, cell. Therapy. Now why is that interesting. So. I'm in the transplantation. Field. And. Transplantation. Has been a wonderful, advance. And. We're, very proud of the, we're. Doing but. If you take a really big picture, look we. Only serve, 10%, of the patients who need, an organ, so. Most patients, die, waiting. That is the reality. It's. A reality you don't hear about very. Much you, you, hear about the. Successes. Going on in the 10%. Of patients who receive, organs. But a lot of. Patients. Do not receive, the organs, that they need so, with. Regenerative, medicine. Transplantation. Using. Stem, cell generated organ stem cell repair door organs. Bioengineered. Organs, you could provide organs, for, everyone.

Assuming. That. The. The. The cost, comes, down to something reasonable. And. How. Many lives would that save a year but, 1.2. Million, people. Need. An an organ. To. Sustain. Life each year, so we. We only serve. 10%, of this number, so over 1 million people, would be saved each year, if we were able to provide organs, to, everybody, that. Need. Them how close, are we well it depends on the kind of organ. Structurally. Simple, organs. We're. Pretty, close we've been able to do, stem-cell, generated, bladders, for some time trachea. Esophagus. Vagina. But. Other, more, complex. Organs. It. Clearly, will take some time before we, able to recreate, the whole organ, but. Even those the present time we can create, organoids. Which, are little like pieces. Of the organ that that, have all the parts but, they. They don't completely, function, because they don't have the major you, know connections so like a liver. Organoid. Would be doing the things that normal liver cells do but. Doesn't have connection. To you, know the bile ducts and all all, that kind, of thing but it still. Can be useful, the. Organoid. Constructs. Can be useful in. Testing. Toxicities. What compounds. Are toxic, various. Organs. So. You don't have to use living. Animals, for that then. So. This, is that. Paper. Of mine from this, month. And. The, other thing that might excite you about this is there are a lot of people your age on, the, author. Line, I'm quite. Proud. Of that but. The. Second. Third. Fourth. And fifth. Author. Are. All. In. Their 20s or, early 30s, so. Anyway. That, happens oh. That's. Kind of the, deal and. Clearly. The, human cell Atlas is an important, part of what I'm talking. About here, it's mentioned in in, the, abstract, in, collaboration. With the human cell ant atlas project there. Are only two abbreviations. In the. Article, and one is in a relation, for the human, cell Atlas. Project. So on obviously, that, is, an important, part of this so. Why is, it. Important. Well as. I. Said there's, something missing. In the concept. Of tissue. Engineering pathology. And. That. Is no knowing what kind of cell should be there how many cell types how, many cell types are necessary. To. Sustain. Life. And, it. May seem simple. But it's, really. Not so. For, a long time it's been thought that in the kidney, there are 26. Cell. Types, but. You notice that this is quite an old articles. From 2002. That. 16. Years. Ago the, other thing that you'd, find kind of charming, about it it's an exceptionally. Well-written, article no, matter what vantage, point you are coming. From you'd find the writing. Of this. Fascinating. You would learn a great, deal from. It so, I I, think that's one, of the reasons that it's still widely. Referred. To but sometimes a very good article. Kind of stops, science. Because people, think this. Is it you know just like in the previous, century. Physics. Reached the point where, people thought well we've learned everything that there is is, to know an article, like this I think gave people the impression, there, really are 26, cell types in the kidney. And that's it and so we have that knowledge and you know we'll just move. On from here. So. Um. It's. Interesting, you. You may think this number. Of 26, is sort of arbitrary, it, is the number of. Different. Letters in, the alphabet. 26. Of if, you look at white cell types if. You go, to any standard, reference, just count up the number. Of white cell types. That. Also. Turns out to be. 26. So. How. Are we going to figure. Out so. Now we're we're able, to. Do. Single. Cell. RNA. Transcripts. - to determine the, genome, of. Individual. Cells telling, you not only. What. The cell is but. Its state. Its. Lineage. You. Know lot lots of other things not, only about what, type of cell it is but, what state of, activation. It is if. It's a cell that commonly. Commonly. Divides, you know how close it is to, to. That point and. So. On so you can tell a lot of things so. One. Interesting. Study. They applied the human cell atlas. Analysis. To. A subset. Of white cells. Dendritic. Cells, and monocytes. And. The, in the original. Understanding. Of the white cell, population. In human beings it, was believed that there were six cell. Types and, after. They completed, the human so atlas. Analysis. And reclassified. There were 12. So. I think this is the most conservative. Evidence. For, what the magnitude, of the impact of the human cell. Atlas could. Be, and. That is that in every organ, in the body, the. Number of cell types we thought, were there is actually, now, double. There is at least twice, as many as. We thought before, and if. You think of the impact of that whatever your favorite, organ, is the impact, of that is probably, huge, that, that. Because. Of this feeling, that you, know whatever organ.

You're You've, been interested in it's kind of like physics. And you know. A century. Ago where people thought all knowledge, was known, and, so on so. We. Thought we knew what all the cell types were and and you know everything, was being analyzed, on the basis, of those cells. So we. Presume, that for, instance in the kidney, if, you. Double the. Number. Of types, that would be going, to 52. And. And. And so maybe there are 52, major. Cell. Types in the kidney, 52. Major. Cell. Types in white, blood cells and, so on I don't. Know whether, young people today knew know about this book still Hitchhiker's. Guide to the. Galaxy. The last group of young. People I talked to, 25. Percent knew. About this book but anyway this. Book, contains. The claim that the, meaning of life the universe and everything is, 42. So. I'm, saying that maybe it's actually, 52 if you use the human. Soul atlas. So. There. There are probably thousands, of, some. Types and, and. So. The the number, of cells the number of types is, large. But finite and. Also. Definable. And one assumes that, in, the next few years as. The human, cell atlas project plays. Out we will be able to define. All, of this, if. You just think about the, kidney, just because I spent time, thinking about, the, kidney if you wouldn't mind thinking, about it for just a short time. Kidney. Medicine. Today a lot. Of it is based on. Examination. Of the urine. Urinalysis. Which. You may know has a 6,000. Year history, just, think, about that for a moment, it's, like the earliest, area, of laboratory. Medicine you. May know that language. Is only 5,000. Years, old, so, this ante, dates by a thousand, years language, so people were drawing. You, know, urine. Containers. And, you know analysis. Of the urine for, a thousand, years before we had written. Language. And. So. There there there. That's. One, side but one presumes, that. You. Could get much more information, about. Patients. By, analyzing. The cells coming out in, the. Urine. This, way doing. So. You. Know genomics, one cell at a time it. Would be. Non-invasive. As you well know it, could be done like, every hour every day. You. Know so if, and, most. People would think that it, would be flawed, because the cells in the urine are mostly dead but that's not true the cells in the urine are mostly alive. They can be grown in, culture. They're, not that different. From. The cells that, that that, are healthy, in you. Know the kidney you are constantly, shedding cells, into. The. Urine and it's. Just that the. Way that we analyze the urine today. Is so. Nonspecific. And vague. That. It's. Just not an, important, means, of coming to any final, answer, usually. And. If you think about the kidney, biopsy, which is my, area of work, my, day. Job but I'm not teaching.

This Course is. That. We've. Been using the same three modalities. Of examining. The biopsy, for, a very, long, time probably. The most recent, change. Was. To begin, looking. For a molecule called c4d. And that occurred in the late, 90s. So. At least you, know twenty, years ago and then. We started, doing. Immunofluorescence. About. Sixty. Years ago. You know electron, microscopy, 70, years ago so the, three. Three. Modalities. Used. To, examine, the kidney biopsy, are very old. And one could could, imagine that what, you would do with a portion. The biopsy, is. Basically. Disaggregate. The cells so you had a solution. Of, single, cells put. Them through this. Microfluidic. Device, and. Get this, single-cell, analysis of. A large number of cells and I I think it probably could quickly tell you much more than. Any of the other ways, that we're, currently looking, at, kidney. Biopsies. So. It. Could. Revolutionize. And. Make much more precise, the, diagnosis. Of kidney, disease, what. About other organs I think, it's absolutely, the same for, every, other organ, any area, of medicine. Or, you. Know science. Of the human body that might interest you I think this would have a huge impact and, make all the data much more precise. It. Is very, quick. You're. You're limited by the speed, of you know. Computation. So. The cells are just. Whizzing. Past you're, you're, getting, these single, cell, analyses. Of. Individual. Cells. But. I think there's there's, no reason to think that it that it won't continue to. Speed. Up. So. Let me just. Yeah. So, we. Frequently. In this course, talk about Moore's, Law, price-performance. Of computing. You're aware. Of the concept, of exponential. Change. But. Actually the, change is going on with the human cell. At lists are much, more rapid, than, this so this curve. Which. Predicts. That, machines, will be smarter, than individual. Humans, in 2029. And smarter. Than the whole aggregate. Human race in 2045. This. Degree, of change is, a. Doubling. Every, two years. So. Now if we compare that. It's. This recent, paper Moore's, law and single-cell. Transcriptomics. In, other words in in the human cell Atlas. Project. So. This, scale. One. Ten, hundred, thousand. Ten thousand, hundred thousand. Million. You can see that in two thousand nine he could only do one cell at, a time it, was very laborious. And. So. I so, you were limited, to. One. So. By. 2010. Sometime, you, could do dozens. Of cells and. By. 2011-2012. You got, 200 and now. We're, up to nearly. Nearly. A million probably, by 2019. We'll be able to do a million. Cells, at a time. So.

I'm, Sure because you're taking this course and you know the course has a lot of Moore's. Law and stuff that you're very impressed, by Moore's. Law but if you compare the two, this. Line here, would be the, Moore's Law change, in other words doubling, every two, years and. This, is what is actually, happening. With. Single. Celled. Transcriptomics. So. It. Is accelerating. Much more quickly, than, that, and, it's kind of exciting to think of something, that's like an. Exponential. On, top. Of another. Exponential. So. And. I don't want you to think there's anything particularly. Renal, or kidney or, in it about the, impact, I think, it will have a similar impact every. Single organ, and, of. Course it won't just be in. People. I I have a human medicine, orientation. But it will. It. Will impact, all. Living. Things, and so. It. May, surprise you, to know that there's a lot of activity, going on here at, the U, of A related, to regenitive. Medicine not. Only the, things. That I have. Been doing. But. For. Instance the vias i'ts trial, the. This. Is an, encapsulated. Pancreatic. Progenitor. Cell that. Is. Used to treat. Type 1. Diabetes. We are one of the major clinical, sites, for that the studies going quite well and dr. James Shapiro. Here. In the Department of Surgery, is one of the lead-in. Investigators. So. Regenerative. Medicine would, be pretty easy maybe, to, conceptualize. If. Everything, about it was positive. But. It's not. There. Is stem-cell frauds, them. Sell high. Intellectual. Dishonesty. And. In stem-cell, medicine. Probably greater than that in any. Other area, of. Medicine. So there, it it's. Kind of hard to. Put. Everything you know about stem. Cell. Research. Together. And to come just, one, you know opinion that you like it or you don't like it or you're in favor of, it or you want, to be a part of it or you want to stay you know away, it's. It's, an interesting intellectual. Challenge. It's, like in. The. Book 1984, the. Idea of. Doublethink. Doublethink. Is holding, two. Conflicting. Ideas in, your mind at, the same time, and, accepting. Them both. Sounds. Like it's not, possible. But but we really do do things, like that I guess, you'd say it's. You. Know provisional. Acceptance right. We're. Balancing. Bank and for between, these two, conflicting. Ideas. And. In. Regenerative. Medicine, it's. Like, more than two ideas. Your your you're. Trying trying, to sort of decide well, given. The reality, they that exists, you know what part should I play in this what should I do and. So. On it is possible. To figure. That out but. We. We, have found that, it's a bit too complicated. To, get people, to voluntarily, come, into a room like if you got to speak to the, general. Public. You need something, else to, interest. Them and, what. We've been doing is incorporating. This in poetry, and music. Because if you just give, a lecture, people. Just, won't, stand. For it I mean you're not giving a clear. Answer, what, do you mean that this is the greatest, hope for the future of Medicine, it's, the area where the greatest, intellectual, dishonesty is, and there's a stem cell tourism. With people going to these, poorly, documented, clinics. In the third world and there, there's, you know the whole you know celebrity effect, and you're, probably all you. Know guilty. Of this you all have like a favorite.

Celebrity. Or sports, star and if that person goes to some, clinic somewhere and gets an injection, and comes back and says it's, the best three things, since sliced bread then you'll wanted to and so it's, a very complicated. World, so. Somehow, rather. Than just lecturing, about this stuff. If you incorporate, it in a sort, of entertaining. Evening, you can get people to start thinking about, it in a way that they might otherwise, not really stand. Or sits still. For so. Timothy. Caulfield. In our health law. Institute. Here at the U of A is like the world's, expert, on. The. Stem. Cell hype the the you, know celebrity, effects. This. Is a huge, issue. Like, if you think about autism. And. The. Belief. That vaccines. Are somehow related. To that that has no basis, in science, but. It has a basis, in you, know good-looking celebrities. Telling, you this right and that's. Like a force, that you would think would, have no influence, on you whatsoever, but, it. It, seems to to. Influence people. Much more than one might like so. This. Is just some of what the. Health. Law. Unit. Here some of their recent. Publications. Combating. On unlicensed, stem-cell. Interventions. From Kim Kardashian. To dr. Oz future, relevance, popular, culture. So. On. So. Forth and. Timothy. Really, is like the world's, expert, in this and. So. That is also here at the U of A. And. There is another way to think about this. That. Is that, within medicine. The areas. That. Attract. Young people, vary. Over time, in. The 60s, 70s, the, 80s there, was nothing. More appealing than. Kidney, medicine, and, you know transplantation. Transplant. Surgery. It. Was just amazingly. Exciting, and the best and brightest young people, wanted, to get, into those fields. And, now. It's considerably. Different. There there is worldwide. Difficulty. Interesting. Young people in, kidney, medicine. Transplantation. Most, people choose, some other field, and, I. Think. That, regenerative, medicine will probably, change, that, because. Once the basic thought is that. We can provide this benefit, to everyone. It becomes. A much more satisfying. Field, to to. Be in then. The. The, idea that. You know we're constantly making, these ethical. Choices between. People. And not worrying about the fact that in some countries you can't get this kind of therapy. At all and and. So. On if if, you. Were doing something that provided, uniform, benefit. Throughout. The world to everybody who needed, it it would be a much more satisfying, area, to be in. And. I. Think. The other way, way, to think about this is your personal. Involvement. You. May be sitting here thinking what, me I'm. Nothing. To do with this but. Likely. You have a skill, or an, interest, that could, be applied here, and making regenitive. Medicine, successful. Is in. Every human beings, interest, and, if, we all assume, that, we're waiting for somebody else to do it and then you, know tell me when it's done and. Then. I'll come. Back then it's going to take decades, to, really make this. Successful. And, you, know worldwide, in, in. Impact. So. It. Is likely that there is something, you could do, and. It's. It's challenging. Enough. This. Is kind of a joke or an attempt, at humor but. A lot of people are worried, about technological. Unemployment. The. Things I've talked about it up until now are complex, enough that you can imagine that. Machines. Might have a little bit of difficulty. Figuring this all out. It's. Still gonna be a role for, human. Beings human you know physicians, and so on here maybe. Kidney. Medicine. Doc's. And, renal, pathologists, will be only people, still employed, in 2045. So. This is the BAMF, classification. Of, allograft. Or transplant, pathology, that I, developed. 27, years, ago this. Is the logo for it. And. Maybe. The first thing you might be interested. In kind, of boring listening. He's. Been, in this for such a long time so what do the young doctors, think of this and so. We this, histologic. Scoring, where we take this very the the various. Changes. You. See under, the microscope, and the kidney and score them on 0 to 3 plus and. So. Our. Youngest. Kidney, pathologist. Who's. Just joined the faculty, says, use of the BAMF classification. Gives. You the imprimatur. Of. Being. An educated, transplant. Pathologist. It's. It's proof that you know, what you're doing so. Anyway. That that's, that's. What he says. About it do you know that word. Imprimatur. It, comes. From printing. Term let. It be printed. It's. The origin, of that so. These are like the highlights, and a banth, classification. It. Was without any structure, whatsoever, until 2013. And when. My. Colleague. Lorraine, rakha, son and I, we. Sort. Of. Managed. It, almost. Like a family. Thing. Without any, society, or any rules or, stuff.

Between 91, and, 2013. In, 2013. We, established, a non-profit. Swiss. Fount. Foundation. So I'm currently the chair of that. Foundation. And I, sat down in 2019. And will be replaced, by Michael mingle, at that time. Surprisingly. For something that is. 27. Years old the. Number of publications. About, it. Continues. To. Go. Up you may know that this institution. Is 6th in the world in terms, of its ranking, for. The. Scientific, area of. Transplantation. Is largely, on the basis, of the literature. Citations. Of, the Banff. Classification. And. You'd, imagine, when we add. Tissue. Engineering, pathology, to that that the number of, citations. Will even go, up. You're. Probably wondering, now what I. Test. You on these slides, no, I'm not gonna test you on these slides I just think you you know this is me this is what I've been, doing I thought you'd be interested in, it but, you're, not going to be tested, on on this slide but, it is a, you. Know consensus. Process. That. Is. Moderated. By. Experts. That's pretty unusual if, you look in the books how, to generate, consensus. Every, book tells you you get a professional, facilitator. Whereas. No stake in the game knows, nothing. About the area bring him in he'll tell everybody this new, way to think and they'll put post-its, on the board and magically. Consensus. Will come about that's never the way that we've done, it but. If, experts. Are moderating. Consensus. You have to be somewhat humble, if somebody else in the room has a better idea than you and, if, the will of the. People. In the room is to go with that person's, idea, you have to accept that people are going to do that rather than coming in with a macho, idea that, your. Way or the highway or you know that that. You. Are much smarter. Than anyone else and should always, dominate. The process, I would absolutely. Kill. It so this is kind. Of a diagram of the way it's been working these are the, people. In the various roles, so, I have organs. Specific. Committee's program. Committees. For each meeting every two years and traditionally. Young. People have played a very important, role in these meetings. Because. In. 2007. I I lost, major funding, for the professional. Staff, Lance, so the. Templates. What the people were doing was very well. Established. So. I just got rid of these highly paid, professionals. Got students. To do the same thing paid them hardly anything, but they were doing this awesome, stuff no. One else in the world was doing and it's. Been working very well since. 2007. So the success, of this. Is, owing, to the efforts, of many. Young, people like yourselves, these, are pictures from the Baths meetings. And, this latest one was in Barcelona Spain. So. The. Idea. That regenerative. Medicine is reality. Now. Is. Something. That there is some. Resistance. To but this is the best Journal, American, Journal of, transplantation. And when this appeared, on the cover in. November. 2014. People. Who had been resisting, thinking, about regenitive, medicine realized. That the jig was up and, they they, they needed to start thinking, about this because this must be a reality. If it's if it's on the cover and. So, I think to a certain extent that that is true and I'm one of the major, forces, that, it keeps you, know reminding. People. About this so I've been talking about this since. My. First after-dinner. Speech in. 2011. So, so, that's like, seven, years and, now. It is, more and more tangible. Reality. So, we have to think about, addressing. Organ. Dysfunction and. Organ, failure. In this way of thinking, of. Cells like. Stem. Cells or. Organ. Progenitor, cells. Scaffolds. For them to grow in bioactive. Factors, so they do the right stuff and grow the right way and then. A bioengineered. Organ. Brought. About by, these tissue, engineered. Constructs. And. I. Keep asking about this slide whether we still need it the idea of jump-starting. The idea that in every audience there'll be resistance. People. Really. Don't think so, anything to do with them and it's not never.

Going To be a reality, and so on and so on and I, I'm sure that, we do still need, this slide so as soon as we don't need the jumpstart, slide, I will get rid of it so. We. Have to start thinking about how. To keep the cells and, a bioengineered. Organ, happy, and. There. Are some very challenging. Things, that, that I'm sure we'll, get over these hurdles. But. For. Instance it's, hard, in a. Reconstructed. Organ where, you take all the cells out and then infuse, new cells in it's. Hard to get pavement. Of more. Than about 80, to 90 percent of the endothelial. Surface, of the arteries, and the veins and. The. Surfaces. That don't have endothelium. Clot like mads. So everything, else is working fine and you've you've got all the cells maybe in the right places inside. The organ but, you hook it up and the. Main. Vessels. Supplying, the Oregon clot so. That's. Something. We will. Get over but it's obviously, one. Challenge. At the moment. So. You may wonder is this an area that. Canadian, citizens, are interested. In and. Supportive. Of supposedly. It is, from. A public policy. Perspective. Canadians. Are in support of. Lightlife. Extension, and, of. Doing. That through. Regenerative. Medicine. So, early, in the course we talked a lot about the technological. Singularity. In. General. This. Idea, that. In, 2045. Or, earlier. Or later, that. Machines. Will be much smarter. Than we are taking over the future agenda, of the world and we can only have, influence. And understand, what happens if we join. Or merge with them in some way. So. There is an equally interesting. Kind of medical. Singularity. You can think of when, this becomes, routine. Where, when. We need a new organ, we just take somebody's, old, organ, flush out the cells, grow. Up some of your cells and fuse your, cells into that organ. Allow the cells, to proliferate. Find. The right places and stuff and then you have a new organ. That. Is. Completely. Compatible, with you, that you're not going to reject and. Someday. We will be able to do that. So. What. Is tissue engineering, pathology, well things, don't go entirely, well. Thus, far so this, is an animal, model of doing, that, and. In. The. Rat. If, you, flush out the cells and then flush in new cells. And, and, so on. Not. Only do you not get enough cells in the places where you want them but. You, get odd. Phenomenon. Like ordinarily, this is the filtering, unit of the kidney that's called the glomerulus. And. It. Has specialized. Epithelial. Cells called, Poteau sites that, stain for POTUS, in' and. You. Don't ever get POTUS and positive, cells anywhere else, in the kidney but in the bioengineered. Reconstituted. A kidney. You do so you get podocytes wandering. Around in, the interstitial. It's. Just one of many. Abnormalities. That you can find in the bio engineer in Oregon so. There. Are many problems with stem-cell, generated, organs are not being discussed and. Some. Of them are.

Challenging. But a lot of them probably require. A background. Of things that you already know, thinks. That where you could provide part. Of the solution. So. I. Talked. About the first. Line about the, clotting. Of the. Non. Endothelial. Surfaces. Hard, to get right so types, of cells and right places, you. Get terminally. Differentiated, cells. That's hard hard, to to get more of them hard, to identify. Progenitors. Sometimes. And. In. The kidney, you know your. Ability to, concentrate. The urine the reason you can sit in a room like this and, although. The, amount of fluid, going through, your, kidney, is greater than what your bladder can hold you're just fine because you're able to, concentrate, the urine so. You don't, have to like right right, to the bathroom every 10 minutes right but, if. You only had short loops of Henle if you didn't have any long loops you would not be able to concentrate the urine, and. When. You regenerate. Kidneys. That's. Mostly. What you get that it's very hard to, have. Those long loops, of Henley, created. The cells seem. To prefer to take shortcuts. So. You. Could end up with a kidney it can do everything, else but cannot, concentrate. The urine. So. There. Are two ways to think about that, maybe. You could think of a. Bioengineered. Organ, like. A. Device. Right, so. You go into a store and you see the specs, for your new cell, phone and it's, certain features that you want and, apps you want it to have and stuff maybe. A bioengineered. Organ is like that and. You could just accept, that it's really, hard to get a kidney that can concentrate the urine but you would want one that can do everything else so. You. Would accept that and say well we're just gonna deal, with this in some. Other way in. Terms, of the, concentration. Of the urine and, the fact that that, it can do all these, other things that it. Can generate, you know erythropoietin. So. That red, cells are. Generated. It can you know get rid of waste it can do everything except, concentrate. The urine maybe from a kind of you, know device, perspective. That's just, fine, in the early days of bioengineered. Organs, you. Can't expect them to do absolutely everything, that, the native organ does. But. Many, old-fashioned. Questions, from physiology. Things. That you've already learned, in school and maybe you thought this is like old news and you never use that knowledge you you took a test on it and. You. Never need that those. Same questions. Can, are now, interesting. Enough. Are. Interesting. Again and in in trying. To figure, out how to make. Bioengineered. Organs, so. Old-fashioned. Concepts. Like the intact, nephron. Hypothesis. Several, generations stunned myocardium. Contraction. Ban necrosis. Those are all terms for. Things as you might have learned learned about that you think you'll never need the information again but it, it really is. Useful. When, when you're trying. To figure out how to make a regenerative. Medicine. Organ. Work. So. We really are at the very beginning, and it's kind of exciting to think we're at the. Beginning. That's what Richard Fineman said back in, the day it's probably still, true we. Are at the very beginning. Of time for, the human race it's not unreasonable, that we grapple, with problems, there, are tens of thousands. Of years in the future, not. Sure you all believe that but I'm just saying fine, one was probably smarter. Than you are so, he might have known own a bit, more, about life than you, do our. Responsibility. Is to do what we can learn where we can improve the solutions, and pass them on, yeah. Anyway, a lot of other people. Had the same idea that as, long as humans, have lived on earth we're, still at the very beginning, of what could be a very long period, for, for us here and so. We should kind of think about things that way, rather.

Than Thinking, we're near, the end. I. Don't. Know if you know about the. Crystal. Palace in London, it was for, a long time the largest like, glass, lined. Building. And then it burned down and so on I think it's being recreated, in. 2018. But. In 1851. There, was first international. Classification of. Diseases. Presented. At this grand exhibition. Of Technology, at London's, Crystal, Palace, and. That. International. Classification of. Diseases. Was. Tremendously. Death, oriented. Cause, of death time of death. And. I. I, think what, I would like to think about is that, our focus, with tissue, engineering, pathology. Is on life right so, are. The abnormalities. Seen, compatible. With an organ, that will provide net, benefit. To the patient. Will. This organ sustain, life. So. These are just some of the questions. We might ask about our regenerative. Medicine. Construct. Bioengineered. Organ. This. Is. A rat. Model. Of. Bioengineered. Kidney, and this. Is a kidney, tubule. Looks. Very different from a normal tubules. Got these multiple. Interconnecting. Paths, and. Down. Here is. Glomerulus. With hardly any cells, in, it, disordered. To bill for. Formation, and. Cynics. Have said can you call this a kidney, well of course you can it has all the usual things got, two wheels go where you lie there just a bit funny-looking, right so rather than insulting, the organ and saying that's, not, a kidney, I think. We should try to figure. Out how to make such. Our organs. Better. And to figure out what the threshold, is for, when they would provide net, benefit. To the patient. These. Pencil. Sketches. Were done by Corey, Fung whose. Student. Approximately, your. Age and. We. Did. Them with the idea that the, journal, would have, a professional. Artist recreate. Them in color but, they decided to rush the article into print so those are the pictures that you'll see his. His, original, pencil. Sketches. Are the art that's in the article, so. This. Shows that this, idea of the short, loops of Henle that could not concentrate, the urine the lung. Loops. Of Henley. Okay. And what.

About The, chance. Of, neoplastic. Transformation. That. Means the, creation of. Malignant. Tumors. The. Classification. Should have, reproducible. Categories. Generalizable. Concepts, not just one-off, kind, of, accidental. Things that happened and. Tissue. Engineering pathology, has been, and. Unnamed, kind. Of area, for, a long time there's been literature. About the reaction. Scaffolds. For growing, cells and, so on but it's been pretty dull kind. Of like in the movies where the cop says move along nothing to see here you know but, now it's, it's, it's. Getting more, interesting, with. Lives. Hanging. In the balance kind, of thing, so. Ladies, and gentleman that's that's, the end of the lecture and. In. Addition to answering questions about the lecture I be. Happy. To answer questions about, the. Midterm. Also. If you wish so, any. Questions. Ok, the midterm. Is is on, 27th. It's a combination, of. Shorter. Short, answer and. Multiple-choice. It. Is somewhat, similar to, the. Quiz, that's got in the first day and some of the questions. Are, the same as, in. That quiz. And. It's, it's, it's, a. Little. Bit longer than. In previous years because the students actually complained, that the. Test was too short that they knew more than the, test was actually measuring. They felt cheated. Okay. I'll. Fix, that yeah. So, that, the test used, to take about 40, minutes, and then we all stood around looking at each other for the rest of the time or there's one, student, taking 80 minutes and the other students, wondering, what's, wrong with that guy kind of thing. So. Now the the, the, exam. Will probably take you about, 60. Minutes, something. Like that it's. A kind of you know benign. Process. I think, most. People are shocked, at how low their, raw, score is and then pleasantly. Surprised, with how high. They're you know corrected, score is once we do the. Scaling. And I've, not received any like threats, of people to I understand. You've been scaling, the grades in that course we, want to talk to you know maybe. Like. You. Know benign, thing, that. People. Are not not, upset about. So. Any. Questions. Does. Single-cell. Genomics, it. Was is this something you'd heard about in any other class or, late night party, or on. Facebook. Or is this your first ever exposure, to the idea of human. Cell atlas. Yes. Wow. Well. I'm glad I told you not now, you know you, know so, yeah. If you, search for that on. Facebook. You'll you'll, find zillions. Of links. And if, you, search, for it in meeting, programs, you won't find any so. It, it is kind of an interesting. Puzzle. At the moment. Yeah. Oh I. Was very pleased at. How you, know engage you, you were on. Tuesday. I think somehow Patrick's, had. Exactly the right nerve but. I would point out that none, of the other lecturers. Are capable, that I think although maybe you, know Gary is so. Patrick. Sam on the on the back of a chair most, of the time leaning, backwards, so you, you could imagine that most of his weight was. Balanced, on that. Side of the chair but he didn't, fall over once and. He just kept doing, that I'm sure, that's not the the, only reason, that the students remained you. Know engaged but, it's funny him so physically. It at, at risk kind of the whole time and. He's. Very, paranoid. About these. Screens. I guess, he's been seriously. Frustrated. By them so. He just came in and decided to do the old-fashioned, writing, on the. Board kind, of kind of thing and, then he sent, them out on a forced march to measure things in the hallway, and so on and then they had to come back and and. Report. And for this group of students. That's. Absolutely. Right, I don't know somehow they. All looked happy. And like finally, this this course was doing what they what, they wanted so what what was it like for you why did it work, so well. Was it do. You have other classes. Like that I mean do you have other profs who sit on the back of their chair and look like they're going to fall, over backwards but, don't, is that a common, thing the profs do these days or. Oh. Okay. I. Didn't, think it was either, and. I don't, think my my, insurance would actually, cover, me. Yes. High level of trust in the chair yes, and. The engineered ability, yes, yes. Yeah. I think. Those. For the ethics. Lectures, in the course which are next month right. A lot of the material, you gave today is water. For consideration. And. The. Ethical, angles, of the future of Medicine. This. Is a good illustration of, what we're dealing with we're. Trying to make ethical decisions both, how to wield, this technology. But. It's always changing, and continues, to change I think one of the fundamental questions is how do we develop a sense of setting. Up a system that will guide us in the right direction, it's. Something that's always changing you know yeah we, thought there were six cells but, then we know that there are 12 and, we.

Can Recently suspect, there might yet be a whole, bunch to be discovered, yes. It. Makes us question how much do we know right now yeah, and. The. Other way to think. About this I I would urge you all sometime. In the next 20 years, watch. Lesley. Cormack. Lecture. In this course she's, the. Dean. Of Arts and, she, only spoke here once but it it's it's, really moving she only has 16, slides, I thought, boy it's gonna be a completely, inadequate, lecture. Who would ever come to class. With 16, slides, but. What, she basically, does. Is, tells, you what medicine. Was like in the Middle. Ages and. Convinces. You it was as complete, as medicine, is today. There. Were answers, to every question there. Were therapies. For everything, you might. Present. With you might think, that it's, completely. Bogus and, there's no basis, for any any, of the, therapeutic. Decisions made. But. There is an outside, chance. Justice. You. Know Gary Goldson. Saying now that maybe. Some of our therapies, today. Are similarly. We think we know why we're doing it but maybe it's entirely, wrong, you know and. You. We, I think most, people had the idea that living, in the Middle. Ages you, kept thinking, if, only my doctor, knew more you, know if only these, things have been discovered, but, nobody was thinking that it's all they thinking. About I wonder if I have the right humerus, you know I wonder, if my, friend died because, you. Know black magic, white magic trying, to figure out what kind of magic it was you know and and. So there there were theories there, there that there were ways of explaining, practically, anything, that could happen to you and a. Variety of, different ways of. Treating. And. As as bad as it may seem like, the outcomes. Weren't. All that good the fact is that people kind, of believed, in that stuff just like we believed in the medicine, of, today. So it is sobering. To. Realize. That. Our medicine. Today which. We're very proud of we. It's, so more complete, in a sense than medicine. Of the Middle. Ages which. Also. Was a, you. Know complete. System. Yeah. Any. Other questions. Yeah.

2018-02-23 04:27

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