So let me just start with my story. So I tore my knee joint meniscus cartilage playing soccer in college. Then I went on to tear my ACL, the ligament in my knee, and then developed an arthritic knee. And I'm sure that many of you in this audience have that same story, and, by the way, I married a woman who has exactly the same story. So this motivated me to become an orthopedic surgeon and to see if I couldn't focus on solutions for those problems that would keep me playing sports and not limit me. So with that, let me just show you a quick video to get you in the mood of what we're trying to explain.
Počeo bih sa svojom ličnom pričom. Igrajući fudbal na fakultetu, povredio sam hrskavicu meniskusa. Potom sam povredio svoj ACL, ligament kolena i razvilo mi se artritisno koleno. Siguran sam da mnogi od vas u publici dele istu priču. Uzgred, moja žena je doživela istu stvar. Sve ovo me je motivisalo da postanem ortoped i da proverim da li bih mogao da se skoncetrišem na traženje rešenja za ove probleme koji bi mi omogućili da igram fudbal i ne bi me ograničavali. Imajući to u vidu, sada bih vam pustio kratak snimak kako bih vam približio šta želim da objasnim.
Narrator: We are all aware of the risk of cancer, but there's another disease that's destined to affect even more of us: arthritis. Cancer may kill you, but when you look at the numbers, arthritis ruins more lives. Assuming you live a long life, there's a 50 percent chance you'll develop arthritis. And it's not just aging that causes arthritis. Common injuries can lead to decades of pain, until our joints quite literally grind to a halt. Desperate for a solution, we've turned to engineering to design artificial components to replace our worn-out body parts, but in the midst of the modern buzz around the promises of a bionic body, shouldn't we stop and ask if there's a better, more natural way? Let's consider an alternative path. What if all the replacements our bodies need already exist in nature, or within our own stem cells? This is the field of biologic replacements, where we replace worn-out parts with new, natural ones.
Pripovedač: "Svi smo svesni rizika za oboljenje od raka, ali postoji još jedna bolest od koje će zasigurno oboleti još više ljudi: artritis. Rak može da vas ubije, ali kada analizirate brojke shvatite da artritis uništava više života. Ukoliko pretpostavimo da ćete dugo živeti, imate 50% šanse da obolite od artritisa. Starenje nije jedini uzrok artritisa. Regularne povrede mogu uzrokovati decenije bola, do momenta kada naši zglobovi bukvalno postanu nefunkcionalni. Očajnički tražeći rešenje, okrenuli smo se pravljenju i dizajniranju veštačkih delova kojima bismo zamenili istrošene delove naših tela, ali usred ove moderne popularizacije potencijala bioničkog tela, zar ne bi trebalo da zastanemo i da se upitamo da li postoji bolji, prirodniji način? Hajde da analiziramo alternativno rešenje. Šta ako rezervni delovi koji su neophodni našim telima već postoje u priordi, ili se nalaze u našim matičnim ćelijama? Ovde govorimo o biološkim zamenama, gde zamenjujemo istrošene delove novim, prirodnim delovima."
Kevin Stone: And so, the mission is: how do I treat these things biologically? And let's talk about both what I did for my wife, and what I've done for hundreds of other patients. First thing for my wife, and the most common thing I hear from my patients, particularly in the 40- to 80-year-old age group, 70-year-old age group, is they come in and say, "Hey, Doc, isn't there just a shock absorber you can put in my knee? I'm not ready for joint replacement." And so for her, I put in a human meniscus allograft donor right into that [knee] joint space. And [the allograft] replaces [the missing meniscus]. And then for that unstable ligament, we put in a human donor ligament to stabilize the knee. And then for the damaged arthritis on the surface, we did a stem cell paste graft, which we designed in 1991, to regrow that articular cartilage surface and give it back a smooth surface there. So here's my wife's bad knee on the left, and her just hiking now four months later in Aspen, and doing well. And it works, not just for my wife, but certainly for other patients. The girl on the video, Jen Hudak, just won the Superpipe in Aspen just nine months after having destroyed her knee, as you see in the other image -- and having a paste graft to that knee. And so we can regrow these surfaces biologically.
Kevin Stoun: Tako da je naša misija sledeća: kako se biološkim putem mogu lečiti ove stvari? Sada ću vam ispričati šta sam uradio za svoju ženu i stotine drugih pacijenata. Pa prva stvar koju bih spomenuo i u slučaju moje žene, a i generalno najčešće to čujem od pacijenata naročito onih koji imaju između 40 i 80 godina, kod sedamdesetogodišnjaka, je to da oni dođu i pitaju: " Doktore, da li postoji neki "amortizer" koji biste stavili u moje koleno? Nisam spreman za zamenu zgloba." Njoj sam uradio alograft transplantaciju i stavio ljudski meniskus pravo u predeo zgloba kolena. To zamenjuje meniskus koji nedostaje. Za rešenje problema nestabilnog ligamenta, implantirali smo humani ligament donora kako bismo stabilizovali koleno. Kako bismo rešili problem artritisa na površini, odradili smo transplant matičnim ćelijama, koji smo dizajnirali 1991. kako bismo regenerisali hrskavicu na površini zgloba i ponovo uspostavili glatku površinu. Sa leve strane možete videti povređeno koleno moje žene, a ovde je vidite na planinarenju četiri meseca nakon toga u Aspenu, gde se oseća dobro. Ovo funkcioniše, ne samo u slučaju moje žene, već sigurno i za druge pacijente. Devojka sa ovog snimka, Džen Hudak, je upravo osvojila "Superpipe" u Aspenu samo devet meseci nakon što je uništila svoje koleno, kao što vidite na drugoj fotografiji, a potom joj je stavljen implant u to koleno, tako da možemo biološki da regenerišemo tu površinu.
So with all this success, why isn't that good enough, you might ask. Well the reason is because there's not enough donor cycles. There's not enough young, healthy people falling off their motorcycle and donating that tissue to us. And the tissue's very expensive. And so that's not going to be a solution that's going to get us global with biologic tissue. But the solution is animal tissue because it's plentiful, it's cheap, you can get it from young, healthy tissues, but the barrier is immunology. And the specific barrier is a specific epitope called the galactosyl, or gal epitope. So if we're going to transplant animal tissues to people, we have to figure out a way to get rid of that epitope.
S obzirom na ovoliki uspeh, možda se pitate zašto to nije dovoljno. Razlog je što ne postoji dovoljno donora tih organa. Nema dovoljno mladih, zdravih ljudi koji doživljavaju saobraćajne nesreće i potom doniraju to tkivo nama. To tkivo je veoma skupo. Tako da to neće biti rešenje koje će dovesti do globalne upotrebe bioloških tkiva. Rešenje leži u tkivu životinja, jer ga ima u izobilju, jeftino je, možete ga izolovati iz mladog, zdravog tkiva, ali tu postoji imunološka prepreka. Specifična prepreka je određeni epitop koji nazivamo galaktozil ili gal-epitop. Ako želimo da transplantiramo životinjsko tkivo ljudima, moramo da smislimo način kako da uklonimo taj epitop.
So my story in working with animal tissues starts in 1984. And I started first with cow Achilles tendon, where we would take the cow Achilles tendon, which is type-I collagen, strip it of its antigens by degrading it with an acid and detergent wash and forming it into a regeneration template. We would then take that regeneration template and insert it into the missing meniscus cartilage to regrow that in a patient's knee. We've now done that procedure, and it's been done worldwide in over 4,000 cases, so it's an FDA-approved and worldwide-accepted way to regrow the meniscus. And that's great when I can degrade the tissue. But what happens for your ligament when I need an intact ligament? I can't grind it up in a blender. So in that case, I have to design -- and we designed with Uri Galili and Tom Turek -- an enzyme wash to wash away, or strip, those galactosyl epitopes with a specific enzyme. And we call that a "gal stripping" technique. What we do is humanize the tissue. It's by gal stripping that tissue we humanize it (Laughter), and then we can put it back into a patient's knee. And we've done that. Now we've taken pig ligament -- young, healthy, big tissue, put it into 10 patients in an FDA-approved trial -- and then one of our patients went on to have three Canadian Masters Downhill championships -- on his "pig-lig," as he calls it. So we know it can work. And there's a wide clinical trial of this tissue now pending.
Moja priča o radu sa životinjskim tkivima je počela 1984. godine. Počeo sam rad koristeći Ahilovu tetivu krave, pri čemu bismo izolovali Ahilovu tetivu krave, a to je čist kolagen tipa I, potom bismo uklonili antigene tako što smo ih razgrađivali pranjem u kiselinama i deterdžentima i uspostavili smo uzorak za regeneraciju. Onda bismo iskoristili tu regenerativnu osnovu i implantirali bismo je u istrošenu hrskavicu meniskusa kako bi došlo do obnavljanja pacijentovog kolena. Odradili smo tu proceduru, i odrađeno je širom sveta 4.000 operacija, to je FDA odobrena (Food and Drug Administration) i širom sveta prihvaćena metoda za obnavljanje meniskusa. To je odlično kada sam u stanju da razgradim tkivo. Ali šta se dešava sa vašim ligamentom kada je meni neophodan netaknut ligament? Ne mogu da ga sameljem u blenderu. U tom slučaju, moram da dizajniram i zajedno sa Urijem Galilijem i Tomom Turekom smo to uradili, enzimatski tretman da operemo ili skinemo, te galaktozil-epitope pomoću posebnog enzima. Ovo zovemo tehnikom uklanjanja gala. Ono što radimo je dodavanje tkivu humanih svojstava. Pomoću enzimskog tretmana, mi ga činimo humanim (smeh), a potom deo tog organa možemo da implantiramo u koleno pacijenta. To smo i uradili. Uzeli smo ligament svinje, mlado, zdravo, veliko tkivo, i implantirali u 10 pacijenata u istraživanju koje je FDA odobreno, nakon toga je jedan od naših pacijenata osvojio tri "Masters Downhill" prvenstva u Kanadi pomoću svog "prasećeg ligamenta", kako ga on zove. Tako da znamo da to radi. Opsežno kliničko istraživanje koje iziskuje ovo tkivo je sada
So what about the next step? What about getting to a total biologic knee replacement, not just the parts? How are we going to revolutionize artificial joint replacement? Well here's how we're going to do it. So what we're going to do is take an articular cartilage from a young, healthy pig, strip it of its antigens, load it with your stem cells, then put it back on to that arthritic surface in your knee, tack it on there, have you heal that surface and then create a new biologic surface for your knee. So that's our biologic approach right now. We're going to rebuild your knee with the parts. We're going to resurface it with a completely new surface.
na listi čekanja. Šta bi bio sledeći korak? Da li bismo mogli potpuno da zamenimo biološko koleno, a ne samo njegove delove? Kako ćemo dovesti do revolucije u zameni veštačkih zglobova? Ovako ćemo to uraditi. Mi ćemo prosto uzeti hrskavicu zgloba mlade, zdrave svinje, očistićemo je od antigena, natovariti je matičnim ćelijama, a onda bismo to implantirali na zglobnu površinu u Vašem kolenu, pričvrstili bismo je tu i ta površina bi se prvo zarasla i potom bi proizvela novu biološka površinu na vašem kolenu. Trenutno je to naš biološki pristup. Napravićemo ponovo Vaše koleno pomoću ovih delova. I obložićemo ga potpuno novim slojem.
But we have other advantages from the animal kingdom. There's a benefit of 400 million years of ambulation. We can harness those benefits. We can use thicker, younger, better tissues than you might have injured in your knee, or that you might have when you're 40, 50 or 60. We can do it as an outpatient procedure. We can strip that tissue very economically, and so this is how we can get biologic knee replacement to go global.
Postoje i druge prednosti koje nalazimo u svetu životinja. Tu su i beneficije napretka u poslednjih 400 miliona godina. Možemo iskoristiti sve prednosti. Možemo koristiti jača, mlađa, bolja tkiva u odnosu na ona koje ste povredili u svom kolenu, ili u odnosu na tkivo koje imate u 40-im, 50-im ili 60-im. To možemo da uradimo bez hospitalizacije pacijenta. Možemo veoma ekonomično da prečistimo to tkivo, i tako bismo uspeli da biološku zamenu kolena učinimo globalnim fenomenom.
And so welcome to super biologics. It's not hardware. It's not software. It's bioware. It's version 2.0 of you. And so with that, coming to a -- (Laughter) coming to an operating theater near you soon, I believe.
Dobrodošli u svet super biologa. To nije hardver. To nije softver. To je biover. Ovo je napredna, 2.0 verzija vas samih. I za kraj, uskoro u, (smeh) verujem, uskoro u pozorištu za operacije u vašoj blizini.
Thank you very much.
Mnogo vam hvala.
(Applause)
(Aplauz).