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)
Pokazaću vam video snimak pojedinih modela na kojima radim. Savršene su veličine i nemaju trunke sala. Da li sam već spomenula da su savršeni? I da su to naučni modeli? (Smeh)
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.
Verovatno ste već shvatili da se bavim inženjeringom tkiva, a ovo je video snimak srca koje kuca, proizvela sam ga u laboratoriji. Nadamo se da ćemo jednog dana ova tkiva koristiti za zamenu organa u ljudskom telu. Danas ću vam objasniti zašto su ova tkiva odlični laboratorijski modeli.
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.
Hajde da porazmislimo o testiranju lekova. Neophodno je da smislite lek, odradite testiranja u laboratoriji, testiranja na životinjama i kliničke studije, tj. testiranja na ljudima, pre nego što lek izađe na tržište. To zahteva mnogo novca i vremena i ponekad, tek kada lek izađe na tržište uočimo mehanizam delovanja koji nije očekivan i šteti ljudima. Što kasnije ustanovimo loše strane, veće su i posledice.
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 pacovi i drugo, bez obzira na sve sličnosti među nama, baš te male razlike između vas i mene značajno utiču na način obrade leka i na to kako ti lekovi utiču 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.
A ako bismo imali bolje modele u samoj laboratoriji koji bi nas predstavili bolje nego pacovi, kao i razlike među nama? Hajde da vidimo kako se to može postići uz pomoć inženjeringa tkiva.
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 za to su takozvane indukovane pluripotentne matične ćelije. Nedavno su razvijene u Japanu. Znači, indukovane pluripotentne matične ćelije. U mnogome podsećaju na embrionalne matične ćelije, ali ih ne prate kontroverze. Indukujemo ćelije, na primer ćelije kože, tako što im dodamo nekoliko gena, gajimo ih i potom ih sakupimo. Prosto možemo da prevarimo te ćelije kože da se vrate u embrionalno stanje, to je kao ćelijska amnezija. Dakle, ništa nije konroverzno, što je super stvar broj jedan. Super stvar broj dva, možete od njih uzgajati bilo koji tip tkiva: mozak, srce, jetru ... shvatili ste već i to sa vašim ćelijama. Tako da možemo da modeliramo vaše srce, vaš mozak 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.
Pravljenje tkiva tačno određene gustine i ponašanja je drugi deo slagalice. To će biti ključno za upotrebu ovih modela u procesu otkrivanja lekova. Ovo je shematski prikaz bioreaktora koji razvijamo u našoj laboratoriji, a treba da nam pomogne da stvaramo tkiva na modularan i merljiv način. Nadalje, zamislite sada masivnu, paralelnu verziju reaktora koji sadrži hiljade delova ljudskog tkiva. To bi bilo kliničko istraživanje 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 prednost indukovanih pluripotentnih matičnih ćelija je u tome što ukoliko uzmemo ćelije kože od ljudi koji boluju od određene genetičke bolesti i napravimo tkiva od njih, onda možemo uz pomoć tehnika inženjeringa tkiva napraviti modele tih bolesti u laboratoriji. Ovo je primer koji je razvila laboratorija Kevina Igana na Harvardu. Oni su proizveli neurone od indukovanih pluripotentnih matičnih ćelija, od ćelija pacijenata koji pate od Lu Gerigove bolesti. Dakle, ćelije su diferencirali u neurone i fantastično je to što su ti neuroni takođe pokazivali simptome bolesti. Dakle, uz pomoć takvih modela možemo se efikasnije boriti nego ikada pre, možemo bolje razumeti bolesti nego ranije i možda možemo otkriti brže i same lekove. Ovo je takođe primer upotrebe matičnih ćelija pacijenata, a ćelije su izolovane iz osobe koja boluje od retinitis pigmentoze. Ovde se radi o propadanju retine. Članovi moje porodice pate od te bolesti i zaista se nadamo da će nam ovakve ćelije pomoći da nađemo lek.
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 sve to dobro zvuči i da su modeli dobri, ali se pitaju: "Da li su zaista dobri koliko i pacovi?" Pacov je organizam, naposletku, tu postoji čitava mreža međusobno povezanih organa. U jetri se obrađuje lek koji deluje na srce i pojedini sporedni proizvodi mogu biti uskladišteni u masnom tkivu. Zar u radu sa tim napravljenim modelima ne propuštate te interakcije? To je drugi pravac razvoja ovog polja. Naučnici to pokušavaju da uspostave kombinujući inženjering tkiva i sistem mirkofluida. Na taj način modeliramo čitav ekosistem tela, povezani sistem brojnih organskih sistema, kako bismo mogli da testiramo način na koji lek koji utiče na krvni pritisak, može da utiče na vašu jetru ili kako antidepresivi utiču na vaše srce. Nije lako uspostaviti te sisteme, ali sada smo na dobrom putu da u tome uspemo, zato pratite novosti.
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.
To nije sve jer jednom kada dođe do odobrenja leka, tehnike inženjeringa tkiva mogu nam pomoći da razvijemo personalizovane tretmane. Možda ćete jednog dana razmišljati o ovom primeru, mada se nadam da se to neće desiti. Zamislite da vas neko pozove i saopšti vam loše vesti da možda bolujete od raka. Zar ne biste pre proverili da li lekovi protiv raka koji su vam prepisani zaista deluju efektivno na vas? Ovo je primer rada iz laboratorije Karen Burg, oni se koriste tehnologijom štampanja kako bi odštampali ćelije raka dojke i tako izučavali razvoj bolesti i njen tretman. Naše kolege na Tufts univerzitetu kombinuju modele kao što su modeli tkivnog inženjeringa, kako bi studirali na koji način se ćelije raka šire od jednog organa u telu do drugog. Možete zamisliti sledeća generacija ovog tipa izučavanja će se zasnivati na čipovima koji oslikavaju mnogobrojna tkiva.
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)
Razmišljajući o modelima o kojima smo upravo pričali možete uvideti da će u budućnosti inženjering tkiva sigurno dovesti do revolucije u procesu razvoja lekova na svakom pojedinačnom koraku na tom putu: modeli bolesti koji će omogućiti sintezu boljih lekova, masivne, paralelne modele ljudskih tkiva koji će u laboratorijskom testiranju smanjjiti broj testiranja na životinjama i ljudima i razviće se terapije podešene prema pojedincu, koje utiču na ono što smatramo tržištem. U suštini, značajno ubrzavamo taj međusobni odnos između razvoja određenog molekula i saznanja kako to utiče na ljudsko telo. Način na koji to činimo u prinicipu potpuno menja biotehnologiju i farmakologiju u informacione tehnologije i pomaže nam da brže, jeftinije i efektivnije otkrijemo i proučimo lekove. Daje novo značanje modelima protiv testiranja na životinjama, zar ne? Hvala vam. (Aplauz)