I'd like to show you a video of some of the models I work with. They're all the perfect size, and they don't have an ounce of fat. Did I mention they're gorgeous? And they're scientific models? (Laughs)
Voljela bih vam pokazati snimku nekih od modela s kojima radim. Svi su savršene veličine i nemaju ni trunke masti. Jesam li spomenula da su prekrasni? I da su znanstveni modeli? (Smijeh)
As you might have guessed, I'm a tissue engineer, and this is a video of some of the beating heart that I've engineered in the lab. And one day we hope that these tissues can serve as replacement parts for the human body. But what I'm going to tell you about today is how these tissues make awesome models.
Kao što ste mogli pretpostaviti, ja sam tkivni inženjer, a ovo je snimka kucajućeg srca koje sam projektirala u labosu. Nadamo se da će jednog dana ova tkiva služiti kao zamjena za dijelove ljudskog tijela. Ono o čemu ću danas pričati je kako ova tkiva čine odlične modele.
Well, let's think about the drug screening process for a moment. You go from drug formulation, lab testing, animal testing, and then clinical trials, which you might call human testing, before the drugs get to market. It costs a lot of money, a lot of time, and sometimes, even when a drug hits the market, it acts in an unpredictable way and actually hurts people. And the later it fails, the worse the consequences.
Dobro, razmislimo na trenutak o testiranju lijekova. Krećemo od stvaranja lijeka, testiranja u labosu, testiranja na životinjama zatim klinička testiranja, koja možemo zvati testiranjem na ljudima, prije nego što se lijek pusti u prodaju. Sve to zahtijeva puno novaca i vremena, a ponekad, čak i kad lijek dođe na tržište, ponaša se nepredvidivo i našteti ljudima. Što kasnije zakaže, to su gore posljedice.
It all boils down to two issues. One, humans are not rats, and two, despite our incredible similarities to one another, actually those tiny differences between you and I have huge impacts with how we metabolize drugs and how those drugs affect us.
Sve se svodi na dva problema. Prvo, ljudi nisu štakori, i drugo, unatoč našim nevjerojatnim međusobnim sličnostima, zapravo one sitne razlike između vas i mene imaju ogroman utjecaj na način na koji metaboliziramo lijekove i kako ti lijekovi utječu na nas.
So what if we had better models in the lab that could not only mimic us better than rats but also reflect our diversity? Let's see how we can do it with tissue engineering.
Stoga, što bi bilo kada bi imali bolje modele u labosu, koji ne samo da će nas bolje oponašati od štakora već odražavati naše različitosti. Pogledajmo kako to možemo postići s tkivnim inženjerstvom.
One of the key technologies that's really important is what's called induced pluripotent stem cells. They were developed in Japan pretty recently. Okay, induced pluripotent stem cells. They're a lot like embryonic stem cells except without the controversy. We induce cells, okay, say, skin cells, by adding a few genes to them, culturing them, and then harvesting them. So they're skin cells that can be tricked, kind of like cellular amnesia, into an embryonic state. So without the controversy, that's cool thing number one. Cool thing number two, you can grow any type of tissue out of them: brain, heart, liver, you get the picture, but out of your cells. So we can make a model of your heart, your brain on a chip.
Jedna od ključnih tehnologija koja je uistinu važna je nešto što se naziva inducirane pluripotentne matične stanice. Razvijene su u Japanu, prilično nedavno. U redu, inducirane pluripotentne matične stanice. Vrlo su slične embrionalnim matičnim stanicama osim što oko njih nema polemike. Induciramo stanice, u redu, recimo, stanice kože, dodajući im par gena, uzgajamo ih, i onda ih pobiremo. Dakle, one su kožne stanice koje možemo prevariti u nešto poput stanične amnezije, u embrionalnom stanju. Stoga, bez diskusije, to je najzanimljivija stvar u vezi toga. Druga zanimljivost je ta da se iz njih mogu uzgajati sve vrste tkiva: mozak, srce, jetra, razumijete, ali od vaših stanica. Stoga, možemo napraviti model vašeg srca, mozga na čipu.
Generating tissues of predictable density and behavior is the second piece, and will be really key towards getting these models to be adopted for drug discovery. And this is a schematic of a bioreactor we're developing in our lab to help engineer tissues in a more modular, scalable way. Going forward, imagine a massively parallel version of this with thousands of pieces of human tissue. It would be like having a clinical trial on a chip.
Proizvodnja tkiva čija su gustoća i ponašanje predvidljivi je drugi dio, i bit će zaista ključno za to da se usvoji korištenje ovih modela u otkrivanju lijekova. Ovo je shema bioreaktora kojeg smo razvili u labosu kako bi pomogao u izradi tkiva na modularnije, skalarnije načine. Zamislite, u budućnosti, masivnu paralelnu verziju ovoga s tisućama ljudskih tkiva. To bi bilo kao da imate klinička ispitivanja na čipu.
But another thing about these induced pluripotent stem cells is that if we take some skin cells, let's say, from people with a genetic disease and we engineer tissues out of them, we can actually use tissue-engineering techniques to generate models of those diseases in the lab. Here's an example from Kevin Eggan's lab at Harvard. He generated neurons from these induced pluripotent stem cells from patients who have Lou Gehrig's Disease, and he differentiated them into neurons, and what's amazing is that these neurons also show symptoms of the disease. So with disease models like these, we can fight back faster than ever before and understand the disease better than ever before, and maybe discover drugs even faster. This is another example of patient-specific stem cells that were engineered from someone with retinitis pigmentosa. This is a degeneration of the retina. It's a disease that runs in my family, and we really hope that cells like these will help us find a cure.
Druga stvar u vezi tih inducirnih pluripotentnih matičnih stanica je ukoliko uzmemo neke kožne stanice, recimo, od ljudi s genetskom bolesti i napravimo tkiva od njih, možemo koristiti tkivne inženjerske tehnike kako bi napravili modele tih bolesti u labosu. Ovdje imamo primjer iz labosa Kevina Eggana na Harvardu. On je proizveo neurone od tih induciranih pluripotentnih matičnih stanica pacijenata koji imaju Lou Gehrigovu bolest, te ih je diferencirao u neurone, i ono što je zapanjujuće je to da su ti neuroni pokazivali znakove te bolesti. Dakle s modelima bolesti kao što su ove, možemo uzvratiti udarac brže nego što smo to ikad prije mogli i možemo bolje razumjeti bolest nego ikad prije, i možda otkriti lijek još brže. Ovo je još jedan primjer matičnih stanica specifčnog pacijenta koje su stvorene od nekoga tko boluje od retinitis pigmentoze. To je degenerativna bolest retine. To je bolest koja se javlja u mojoj obitelji, i stvaro se nadam da će stanice poput ovih pomoći u pronalasku lijeka.
So some people think that these models sound well and good, but ask, "Well, are these really as good as the rat?" The rat is an entire organism, after all, with interacting networks of organs. A drug for the heart can get metabolized in the liver, and some of the byproducts may be stored in the fat. Don't you miss all that with these tissue-engineered models? Well, this is another trend in the field. By combining tissue engineering techniques with microfluidics, the field is actually evolving towards just that, a model of the entire ecosystem of the body, complete with multiple organ systems to be able to test how a drug you might take for your blood pressure might affect your liver or an antidepressant might affect your heart. These systems are really hard to build, but we're just starting to be able to get there, and so, watch out.
Neki ljudi misle da su ovi modeli odlična zamisao ali pitaju: "Jesu li stvarno dobri poput štakora?" Štakor je ipak cijeli organizam sa svim interakcijama organa. Lijek za srce se može metabolizirati u jetri, i neki od nusprodukata se mogu pohraniti u masti. Zar se sve to ne gubi s ovim modelom stvaranja tkiva? Ovo je drugi trend u ovom polju. Kombiniranjem tehnike stvaranja tkiva s mikrofluidima, polje zapravo napreduje upravo prema tome, modelu cijelog ekosustava tijela, potpunog sa raznim organskim sustavima da bi se testiralo kako lijekovi koje uzimate za krvni tlak možda utječu na vašu jetru ili antidepresivi na vaše srce. Takve sustave je teško izgraditi, i tek krećemo prema tome, zato, pazite se.
But that's not even all of it, because once a drug is approved, tissue engineering techniques can actually help us develop more personalized treatments. This is an example that you might care about someday, and I hope you never do, because imagine if you ever get that call that gives you that bad news that you might have cancer. Wouldn't you rather test to see if those cancer drugs you're going to take are going to work on your cancer? This is an example from Karen Burg's lab, where they're using inkjet technologies to print breast cancer cells and study its progressions and treatments. And some of our colleagues at Tufts are mixing models like these with tissue-engineered bone to see how cancer might spread from one part of the body to the next, and you can imagine those kinds of multi-tissue chips to be the next generation of these kinds of studies.
Ali to nije sve, jer jednom kada je lijek odobren, tehnika razvoja tkiva može zapravo pomoći razviti osobniji tretman. Ovo je primjer onoga što bi vas zanimalo jednog dana, ali nadam se da neće, jer zamislite ako dobijete taj poziv koji donosi lošu vijest da možda imate rak. Zar se ne bi ste radije testirali i vidjeli djeluju li ti lijekovi za rak koje će te uzimati na vaš rak? Ovo je primjer iz labosa Karen Burg, gdje oni koristeći se tehnologijom printanja printaju stanice raka dojke i proučavaju njegov napredak i tretman. A neke od naših kolega na Turfu miješaju modele poput ovih sa stvorenim tkivom kosti i gledaju kako se rak širi s jednog dijela tijela na drugi, možete zamisliti čipove s različitim tkivima kao sljedeću generaciju ovakvih studija.
And so thinking about the models that we've just discussed, you can see, going forward, that tissue engineering is actually poised to help revolutionize drug screening at every single step of the path: disease models making for better drug formulations, massively parallel human tissue models helping to revolutionize lab testing, reduce animal testing and human testing in clinical trials, and individualized therapies that disrupt what we even consider to be a market at all. Essentially, we're dramatically speeding up that feedback between developing a molecule and learning about how it acts in the human body. Our process for doing this is essentially transforming biotechnology and pharmacology into an information technology, helping us discover and evaluate drugs faster, more cheaply and more effectively. It gives new meaning to models against animal testing, doesn't it? Thank you. (Applause)
Razmislite o modelima koje smo upravo spomenuli, vidite, napredujući, tkivni inženjirign bi mogao zapravo revolucionizirati razvoj lijekova u svakome koraku svoga puta: modeli bolesti pomažu u boljoj formulaciji lijekova, masivni paralelni modeli ljudskih tkiva revolucionariziraju testiranje u labosima, smanjeno je testiranje na životinjama i kliničko testiranje na ljudima, i individualizirane terapije koje poništavaju ono što smo smatrali tržištem. Zapravo, dramatično ubrzavamo povratnu informaciju između razvoja molekule i proučavanja kako djeluje na ljudsko tijelo. Napredak u tome je zapravo pretvorba biotehnike i farmakologije u jednu informacijsku tehnologiju, pomažući nam razviti i procijeniti lijekove brže, jeftinije i efikasnije. dajući novo značenje modelima protiv testiranja na životinjama, zar ne? Hvala vam. (Pljesak)