Dakle, ja sam neurohirurg. i kao većina mojih kolega, svaki dan se suočavam sa ljudskom tragedijom. Shvatila sam kako se život može promijeniti u sekundi, nakon velikog moždanog udara ili automobilske nesreće. Ono što je veoma frustrirajuće za nas neurohirurge jeste shvatiti, da za razliku od drugih organa tijela, mozak ima veoma malu sposobnost da može samostalno zacijeliti. I nakon velike ozljede vašeg centralnog nervnog sistema, pacijenti često ostaju sa teškim hendikepom. I to je vjerojatno razlog zašto sam izabrala da budem funkcionalni neurohirurg.
So I'm a neurosurgeon. And like most of my colleagues, I have to deal, every day, with human tragedies. I realize how your life can change from one second to the other after a major stroke or after a car accident. And what is very frustrating for us neurosurgeons is to realize that unlike other organs of the body, the brain has very little ability for self-repair. And after a major injury of your central nervous system, the patients often remain with a severe handicap. And that's probably the reason why I've chosen to be a functional neurosurgeon.
Ko je funkcionalni neurohirurg? To je doktor koji se trudi da poboljša neurološku funkciju kroz različite hirurški strategije. Sigurno ste čuli za jedan od najpoznatijih naziva duboka stimulacija mozga gdje se ugrade elektrode u dubini mozga kako bi se modulirao krug neurona za poboljšanje neurološke funkcije. To je zapanjujuća tehnologija koja se usavršila zbog sudbine pacijenata sa Parkinsonovom bolesti, sa ozbiljnim podrhtavanjem, uz jake bolove. Međutim, neuromodulacija ne znači neuronske popravke. San funkcionalnog neurohirurga jeste da izliječi mozak. Mislim da se približavamo tom snu.
What is a functional neurosurgeon? It's a doctor who is trying to improve a neurological function through different surgical strategies. You've certainly heard of one of the famous ones called deep brain stimulation, where you implant an electrode in the depths of the brain in order to modulate a circuit of neurons to improve a neurological function. It's really an amazing technology in that it has improved the destiny of patients with Parkinson's disease, with severe tremor, with severe pain. However, neuromodulation does not mean neuro-repair. And the dream of functional neurosurgeons is to repair the brain. I think that we are approaching this dream.
Željela bih Vam pokazati da smo veoma blizu tome. I da uz malo pomoći, mozak je u stanju da si pomogne.
And I would like to show you that we are very close to this. And that with a little bit of help, the brain is able to help itself.
Dakle, priča počinje prije 15 godina. U to vrijeme, bila sam glavni stanovnik radnih dana i noći u hitnoj. Često sam morala brinuti o pacijentima sa povredama glave. Možete zamisliti da kada pacijent dođe sa teškim povredama glave, natečenim mozgom, njegov intrakranijalni pritisak je povećavajući. A kako bi spasili njegov život, morate smanjiti taj intrakranijalni pritisak. A da bi to napravili, ponekad morate ukloniti dio natečenog mozga. Dakle, umjesto odklanjanja tog dijela natečenog mozga, odlučili smo sa Jean-François Brunet, mojim kolegom, biologom, da proučavamo.
So the story started 15 years ago. At that time, I was a chief resident working days and nights in the emergency room. I often had to take care of patients with head trauma. You have to imagine that when a patient comes in with a severe head trauma, his brain is swelling and he's increasing his intracranial pressure. And in order to save his life, you have to decrease this intracranial pressure. And to do that, you sometimes have to remove a piece of swollen brain. So instead of throwing away these pieces of swollen brain, we decided with Jean-François Brunet, who is a colleague of mine, a biologist, to study them.
Šta mislim pod tim? Željeli smo da rastu ćelije od tih komada tkiva. Nije lagan zadatak. Rast ćelija od komada tkiva je isto što i rast veoma male dijece iz svoje porodice. Tako da je potrebno pronaći hranjive tvari, toplinu, vlažnost i lijepo okruženje da bi napredovali. Dakle, to je upravo ono što smo uradili sa ovim ćelijama. I nakon mnogo pokušaja, Jean-François je to uradio. I to je vidio pod mikroskopom.
What do I mean by that? We wanted to grow cells from these pieces of tissue. It's not an easy task. Growing cells from a piece of tissue is a bit the same as growing very small children out from their family. So you need to find the right nutrients, the warmth, the humidity and all the nice environments to make them thrive. So that's exactly what we had to do with these cells. And after many attempts, Jean-François did it. And that's what he saw under his microscope.
I to je bilo, za nas, veliko iznenađenje. Zašto? Jer ovo izgleda isto kao kultura matičnih ćelija, sa velikim zelenim ćelijama opkoljavajuće male, nezrele ćelije. A možda se sjećate iz biologije da matične ćelije su nezrele ćelije, koje se mogu pretvoriti u bilo koju vrstu ćelije tijela. Mozak odrasle osobe ima matične ćelije, ali one su vrlo rijetke i oni su locirani u dubokim i malim utočištima u dubini mozga. Toliko je bilo iznenađujuće dobiti ovu vrstu kulture matičnih ćelija iz površnog dijela otečenog mozga kojeg smo imali u operativnom pozorištu.
And that was, for us, a major surprise. Why? Because this looks exactly the same as a stem cell culture, with large green cells surrounding small, immature cells. And you may remember from biology class that stem cells are immature cells, able to turn into any type of cell of the body. The adult brain has stem cells, but they're very rare and they're located in deep and small niches in the depths of the brain. So it was surprising to get this kind of stem cell culture from the superficial part of swollen brain we had in the operating theater.
A tu je još jedno intrigantno zapažanje : Redovne matične ćelije su vrlo aktivne ćelije -- ćelije koje se dijele, dijele, dijele veoma brzo. I one nikada ne umiru, one su besmrtne ćelije. Ali, ove ćelije se ponašaju drugačije. One se dijele polako, i nakon nekoliko nedelja kulture, one čak i umru. Tako smo bili ispred nepoznatih novih stanovništva ćelija koja su izgledale kao matične ćelije ali su se ponašle drugačije.
And there was another intriguing observation: Regular stem cells are very active cells -- cells that divide, divide, divide very quickly. And they never die, they're immortal cells. But these cells behave differently. They divide slowly, and after a few weeks of culture, they even died. So we were in front of a strange new cell population that looked like stem cells but behaved differently.
Trebalo nam je dosta vremena da shvatimo odakle su došli. Oni dolaze iz ove ćelije. Ove plave i crvene ćelije nazivaju doublecortin - pozitivne ćelije. Svi vi imate ih u mozgu. Oni predstavljaju četiri posto Vaših kortikalnih moždanih ćelija. Oni imaju vrlo važnu ulogu u fazi razvoja. Kada ste bili fetus, oni su pomogli vašem mozgu da se složi. Ali zašto oni ostaju u Vašoj glavi? To ne znamo. Mi mislimo da oni mogu da učestvuju u popravku mozga jer smo ih našli u većem zgušnjavanju blizu oštećenja mozga. Ali to nije tako sigurno. Ali postoji jedna jasna stvar -- da iz ove ćelije, smo dobili naše kulture matičnih ćelija. Bili smo ispred potencijalnog novog izvora ćelija da bi oporavili mozak. I morali smo to dokazati.
And it took us a long time to understand where they came from. They come from these cells. These blue and red cells are called doublecortin-positive cells. All of you have them in your brain. They represent four percent of your cortical brain cells. They have a very important role during the development stage. When you were fetuses, they helped your brain to fold itself. But why do they stay in your head? This, we don't know. We think that they may participate in brain repair because we find them in higher concentration close to brain lesions. But it's not so sure. But there is one clear thing -- that from these cells, we got our stem cell culture. And we were in front of a potential new source of cells to repair the brain. And we had to prove this.
Tako da bi dokazali, morali smo dizajnirati eksperimentalnu paradigmu. Ideja je bila da se uradi biopsija dijela mozga u ne-elokventno područje mozga, a potom i u kulture ćelija upravo kako je Jean-François to uradio u svom laboratoriju. I onda ih označe, u njima stave boju kako bi mogli da ih prate u mozgu. I posljednji korak je bio da se ponovno ugradi u iste ličnosti. Zovemo ih autologni transplantati - autograftovi.
So to prove it, we decided to design an experimental paradigm. The idea was to biopsy a piece of brain in a non-eloquent area of the brain, and then to culture the cells exactly the way Jean-François did it in his lab. And then label them, to put color in them in order to be able to track them in the brain. And the last step was to re-implant them in the same individual. We call these autologous grafts -- autografts.
Dakle, prvo pitanje koje smo imali, "Šta će se dogoditi ako implantiramo ćelije u normalni mozak, i šta će se desiti ako ponovo implantiramo iste ćelije u ozlijeđen mozak?" Zahvaljujući pomoći profesora Eric Rouiller, radili smo s majmunima.
So the first question we had, "What will happen if we re-implant these cells in a normal brain, and what will happen if we re-implant the same cells in a lesioned brain?" Thanks to the help of professor Eric Rouiller, we worked with monkeys.
Dakle, u prvom slučaju scenarija, mi smo ponovo implantirali ćelije u normalni mozak a ono što smo vidjeli je da su potpuno nestali nakon nekoliko sedmica, kao da su uzeti iz mozga, oni se vraćaju kući, prostor je već zauzet, nisu potrebni tamo, tako da nestaju.
So in the first-case scenario, we re-implanted the cells in the normal brain and what we saw is that they completely disappeared after a few weeks, as if they were taken from the brain, they go back home, the space is already busy, they are not needed there, so they disappear.
U drugom slučaju scenarija, izvršavali smo lezije, ponovo smo implantirali isti ćelije, i, u ovom slučaju, ćelije su ostale -- i postale zreli neuron. I to je slika onoga što smo mogli da posmatramo pod mikroskopom. To su ćelije koje su ponovo implantirane. A kao dokaz oni donose, ova mala mjesta, to su ćelije koje smo označili in vitro, kada su bili u kulturi.
In the second-case scenario, we performed the lesion, we re-implanted exactly the same cells, and in this case, the cells remained -- and they became mature neurons. And that's the image of what we could observe under the microscope. Those are the cells that were re-implanted. And the proof they carry, these little spots, those are the cells that we've labeled in vitro, when they were in culture.
Naravno, nismo se mogli zaustaviti ovdje. Da li će ove ćelije pomoći majmunima da se oporave nakon lezije? Što se tiče toga, obučavali smo majmune da obavljaju ručno spretnost zadatka. Oni su morali da izvade hranu peleta iz poslužavnika. Bili su jako dobri u tome. I kad su postigli plato performansi, radili smo lezije motornog korteksa odgovarajućim pokretom ruke. Dakle, majmuni su plegic, oni više nisu mogli pomjerati ruku. I isto tako bi i ljudi radili, oni bi se spontano oporavili u određenoj mjeri, isto kao i nakon moždanog udara. Pacijenti su potpuno plegic, oni se pokušavaju da se oporave zbog mehanizma mozga plastičnost, oni se oporavljaju do jedne mjere, isto vrijedi i za majmune.
But we could not stop here, of course. Do these cells also help a monkey to recover after a lesion? So for that, we trained monkeys to perform a manual dexterity task. They had to retrieve food pellets from a tray. They were very good at it. And when they had reached a plateau of performance, we did a lesion in the motor cortex corresponding to the hand motion. So the monkeys were plegic, they could not move their hand anymore. And exactly the same as humans would do, they spontaneously recovered to a certain extent, exactly the same as after a stroke. Patients are completely plegic, and then they try to recover due to a brain plasticity mechanism, they recover to a certain extent, exactly the same for the monkey.
Dakle, kada smo bili sigurni da je majmun stigao do platoa od spontanog oporavka, mi smo implantirani njegove vlastite ćelije. Dakle, na lijevoj strani, vidite majmuna koji je se spontano oporavio. On je oko 40 do 50 posto njegovog prethodnog performansa prije lezije. On nije toliko precizan, nije toliko brz. Pogledajte sada, kada smo ponovo implantirali ćelije: Dva mjeseca nakon ponovne implantacije, ista ličnost.
So when we were sure that the monkey had reached his plateau of spontaneous recovery, we implanted his own cells. So on the left side, you see the monkey that has spontaneously recovered. He's at about 40 to 50 percent of his previous performance before the lesion. He's not so accurate, not so quick. And look now when we re-implant the cells: Two months after re-implantation, the same individual.
(Aplauz)
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Iskreno da Vam kažem, to je bio veoma uzbudljiv rezultat za nas. Od tada smo shvatili mnogo više o ovim ćelijama. Znamo da ih možemo sa krioprezervacijom, koristiti kasnije. Znamo da ih možemo primijeniti u drugim neuropatološkim modelima, kao što je Parkinsonova bolest. Ali, naš san je i dalje da ih usadimo u ljude. I zaista se nadam da ću biti u stanju da Vam to uskoro i pokažem da nam ljudski mozak daje alate za oporavak sebe.
It was also very exciting results for us, I tell you. Since that time, we've understood much more about these cells. We know that we can cryopreserve them, we can use them later on. We know that we can apply them in other neuropathological models, like Parkinson's disease, for example. But our dream is still to implant them in humans. And I really hope that I'll be able to show you soon that the human brain is giving us the tools to repair itself.
Hvala Vam.
Thank you.
(Aplauz)
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Jocelyne, ovo je nevjerovatno, i siguran sam da trenutno postoje nekoliko desetina ljudi u publici, možda čak i većina, koji razmišljaju, "Znam nekog kome može da koristi ovo. " Ja, u svakom slučaju. I naravno pitanje je, koje su najveće prepreke prije nego što možete ići u ljudska klinička ispitivanja?
Bruno Giussani: Jocelyne, this is amazing, and I'm sure that right now, there are several dozen people in the audience, possibly even a majority, who are thinking, "I know somebody who can use this." I do, in any case. And of course the question is, what are the biggest obstacles before you can go into human clinical trials?
Najveće prepreke su propisi. (Smijeh) Dakle, od ovih uzbudljivih rezultata, trebate popuniti oko dva kilograma radova i oblika da bi mogli proći kroz ove vrsta suđenja.
Jocelyne Bloch: The biggest obstacles are regulations. (Laughs) So, from these exciting results, you need to fill out about two kilograms of papers and forms to be able to go through these kind of trials.
BG: Što je i razumljivo, mozak je delikatna, itd
BG: Which is understandable, the brain is delicate, etc.
JB: Da, to je, ali to dugo traje i puno strpljenja i skoro stručni tim ti reba da to uradi, znaš?
JB: Yes, it is, but it takes a long time and a lot of patience and almost a professional team to do it, you know?
Ako projekat - završi istraživanje i nakon što je pokušao da dobije dozvolu za početak suđenja, i ako je projekat u vremenu, koliko godina treba prije nego li neko dođe u bolnicu da ova terapija bude na raspolaganju?
BG: If you project yourself -- having done the research and having tried to get permission to start the trials, if you project yourself out in time, how many years before somebody gets into a hospital and this therapy is available?
Dakle, to je vrlo teško reći. To ovisi, prvo, o odobrenju suđenja. Hoće li nam propis omogućiti da to učinimo uskoro? I onda, morate obavljati takvu vrstu studija u maloj grupi pacijenata. Tako da je potrebno, dugo vremena za odabir pacijenata, da se učini tretman i procijeni da li je to korisno za ovu vrstu liječenja. I onda morate razviti to multicentrično suđenje. Morate zaista dokazati prvo, da je to korisno za svakoga prije ponude ovog tretmana.
JB: So, it's very difficult to say. It depends, first, on the approval of the trial. Will the regulation allow us to do it soon? And then, you have to perform this kind of study in a small group of patients. So it takes, already, a long time to select the patients, do the treatment and evaluate if it's useful to do this kind of treatment. And then you have to deploy this to a multicentric trial. You have to really prove first that it's useful before offering this treatment up for everybody.
- I sigurno, naravno. - Naravno.
BG: And safe, of course. JB: Of course.
Jocelyne, hvala vam što ste došli na TED i podijelili ovo. Hvala Vam.
BG: Jocelyne, thank you for coming to TED and sharing this. BG: Thank you.
(Aplauz)
(Applause)