Anthony Atala: 打印一個人的腎臟

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http://dotsub.com/view/6db231a1-3e7b-4b32-8e8c-b49a553cb01a
Anthony Atala: 打印一個人的腎臟
现今社会主要的健康危机， 就是器官短缺。 我们越活越长了。 是医药学的进步 帮助我们越活越长。 问题是，我们越老， 我们的器官越爱失灵。 现今社会， 没有足够的器官来替补。 事实上，过去十年间， 需要器官移植的人加了一倍， 但同时 器官移植手术并没有增多。 所以说这现在是个全社会的健康危机。
这就是我们这个领域的研究要解决的问题， 我们管它叫再生医学。 再生医学包括很多研究领域， 你可以使用，事实上，模子， 加上生物材料—— 好像是从你的衬衫上取下一片—— 但是它们是为了放入人体而特殊制作的。 这些生物材料很安全，还能帮助你自身的组织再生。 或者我们也可以仅仅使用细胞， 或是你自己的细胞， 或是他人的干细胞。 我们甚至同时使用两种技术， 事实上，我们可以移植生物材料 同时一起移植细胞。 这就是当今再生医学的研究水平。
这并不是个新兴科学， 有趣的是，有本书 在1938年就出版了， 名字叫“器官培养”。 书的第一作者，艾利克斯 卡如，是个诺贝尔奖得主。 他发明了一些技术， 今天我们缝合血管的时候还在沿用。 我们今天用的一些血管移植片 其实是艾利克斯设计的。 请大家注意书的另一个作者： 查尔斯 林德伯格。 就是这个查尔斯 林德伯格， 投入了毕生精力， 与艾利克斯一起工作 在纽约的洛克菲勒研究院， 研究器官培养。
所以再生医学其实已经有很长的历史了。 那么，为什么在临床上没有什么突破呢？ 这是因为（在临床上）有很多不同的难关。 我认为前三位的难关， 第一就数材料学， 设计什么样的生物材料，能置入人体 不引起任何问题。 我们已经有了很多突破， 在这方面我们进步神速。 第二个大挑战，就是活细胞。 我们没法得到在体外培养足够数量的细胞。 过去的二十年间，我们就卡在这里。 如今很多科学家已经能在体外养活很多种的细胞—— 加上我们还有干细胞。 但即便是这一刻，2011年， 有些类型的细胞我们就是没有办法在体外养活。 比如肝脏细胞，神经细胞，胰腺细胞—— 即使是今天我们还是在体外养不活。 第三个难关是建立血管网， 有了血液的供给 我们再造的器官或者组织 才能存活。
这里我们就要用到生物材料。 这就是一种生物材料。 我们或编或织，或者像是做棉花糖一样 像你们现在看到的，做出生物材料。 你能看到有喷雾， 就像是棉花糖的糖线， 做出这个框架，很多的管状结构。 这是我们用的 生物材料， 来帮助你身体器官 用你自己的细胞再生。 这是我们做的一个案例。
这是个真的病人， 他有个报废的器官， 我们做了一个挺光鲜的生物材料 用它来 替换下旧的器官， 修补好这个病人的身体。 具体来说我们 用这个生物材料搭了个桥， 这样这个器官里的细胞 就能够在桥上生长， 补上缺口， 这样组织就再生了。 你能看到这个病人的X光片，手术后六个月， 组织的再生， 当你在显微镜下分析时， 能看到这是百分之百的再生。 我们也可以单用细胞移植。 这些是我们得到的真的细胞， 它们都是我们从各种渠道得到的干细胞。 我们可以使它们长成心脏细胞， 它们在培养皿中就能开始搏动， 这说明它们知道该干什么， 它们靠基因中的信息知道该怎么工作。 它们还能同步搏动。 现今许多的临床试验 都在用各种各样的干细胞 来治疗心脏病。 它们已经在病人身上起作用了。
如果我们想一直更大号的人造组织 来替换大块的身体组织， 我们可以使用病人自己的细胞， 或者细胞群， 加上生物材料， 模子，全要用到。 基本上， 如果你的某个器官死亡了，或者损坏了， 我们可以在这个器官上取下一小块， 小到半个邮票的大小。 然后我们把细胞摇下来， 在体外培养。 之后我们将用生物材料做一个模子， 这片材料就像从你的衬衫上取下的一片， 我们可以改变它的形状， 再把培养的细胞涂上去， 一层层地涂—— 就像是烤层层叠叠的蛋糕一样。 当我们把这块“蛋糕”放进“烤箱”， 就能使这个组织重生， 把它取出来用。 这里是我们作出的 真的心脏瓣膜。 你能看到我们先有了瓣膜的框架， 再把细胞种上去， 然后让它锻炼锻炼。 我们可以看到这个瓣膜上 尖瓣小叶开开合合—— 这现在还在试验阶段， 我们希望能很快应用。
另一个我们用在 病人身上的技术是 关于膀胱移植的。 我们能从病人的膀胱上取下一小块来—— 比半块邮票还小， 然后进行体外细胞培养， 在拿个模子，涂上细胞—— 病人自己的两种细胞， 然后把模子放进“烤箱”， 它有和体内同样的环境—— 三十五摄氏度，百分之九十五氧气， 几星期后，你就有人造器官了， 我们能把它们移植回到病人身上。 有些特殊的病人，我们只需要把这些材料缝上去就成了。 我们可以用三维图像系统描图， 然后用手工制作。
现在我们有更好的方法 来用细胞作出器官。 我们现在用几种技术 来做块状的器官，比如 肝脏。 我们的作法是拿个遗弃的肝脏， 要知道，很多器官都被丢弃不用了。 我们把别人不要的 肝脏拿来， 把它们放在类似洗衣机的机器里， 把细胞都洗下来。 两周后 你得到一个像是肝脏的东西 你可以把它托在手上， 但是这个肝脏没有任何细胞，这只是个肝脏的架子。 我们之后从血管 把细胞灌进这个肝脏里。 所以我们其实是先把病人的血管细胞 从血管里灌进去， 然后把其他的组织用病人的肝脏细胞填满。 上个月， 我们才用这个技术 得以成功地 造出了人类的肝脏。
另一个技术是我们以前用过的， 就是打印器官的技术。 这时办公室用的打印机 只是我们不用墨粉 我们用的是活细胞。 你可以看到打印头 左右移动，打印出一块组织， 一般这样的组织要花四十分钟来打印。 另外（这个组织坐在）一个三维升降机（上）， 打印时，每次打印头走到头， 它会（带着这块组织）下降一层。 最后你就能得到整个组织了。 你能把组织取下来，然后移植入病人体内。 这张幻灯片显示的 是我们用办公室打印机 打印出的一片真的骨头， 然后移植入人体的。 这里的骨头都是 用这个技术移植的。
另一个我们正在研究的更为先进的技术， 新一代的技术， 要使用更为复杂的打印机。 这个我们正在设计中的特殊的打印机 能够在病人身上实时打印。 你看吧—— 我知道听起来挺傻的， 但是真的是需要的。 因为现实中你希望做的， 是希望在病人受伤躺上病床上时， 能有一个扫描机 就像是个正常的平面扫描机 你能看到在这里右边； 扫描机能先 扫描病人的伤口， 在把信息传到打印头上， 打印头就在伤口上 实时打印。
这里展示了这个系统是怎么工作的。 这里是扫描机 来回扫描伤口。 扫描完了， 它就会把哪里需要 新的细胞层的信息送出去。 现在你将要看到的 是一个录像，显示了 这个打印机是如何在一个伤口上打印的。 我们其实在打印机里加了胶质，这样你就能把打印的组织提起来， 当你把组织移植到病人身体里去时， 它们也能成功地粘在该呆的地方。 这确实是个新技术， 我们还在研发中。
我们还在研制更为复杂的打印机， 因为事实上我们最大的挑战 是块状组织。 我不知道你注意到了没有， 百分之九十的等待器官移植的病人 都是在等肾脏。 病人天天去世， 都是因为我们没有足够的器官。 所以这正是更大的挑战—— 大型器官，布满血管的， 需要很多的血液供应， 需要很多细胞。 所以这里的策略是—— 这是个真正的CT扫描，一个X光片—— 我们可以层层解析， 使用电脑化的图像和形态分析 以及三维重组的技术， 来观察这些病人自己的肾脏。 我们能够观察这些肾脏， 三百六十度旋转， 这样就能全方位地 研究整个肾脏。 之后我们就能 应用这些信息， 扫描 变成打印出的层层电子图。 这样我们就能层层深入 解析这个器官的每一层， 之后我们就能把信息送出去，像你这里看到的， 送到计算机里去 然后为病人 设计出新的器官 这里是一家真的打印机。 它也在真的打印。
事实上，我们在现场就有一个。 在我们今天演讲的过程中， 你们能看到这架打印机 就在后台。 这就是我们用的打印机， 它一直在打印这个肾脏， 你们能看到。 一般打印一个肾脏要七个小时， 这个已经打印了三个小时了。 康医生将到前台来， 我们将给你看一个我们 今天早些时候打印的肾脏。 让我戴上手套。 谢谢你。 到后面来一点 这些手套有点小，好了 你现在能看到这个肾脏 我们今天早些时候打印的。
（掌声）
还有一点粘。 这是康医生，他和我们一起为这个项目工作 是我们队伍的一份子。 谢谢你康医生，我很感谢。
（掌声）
这就是新一代的打印机， 这个我们在台上看到的。 这是我们正在研究的新技术。 其实我们已经做这个技术很长时间了， 我想和你们分享一个小片段， 关于我们用在病人身上已有一段时间的技术。
这是个很短的片段—— 只有三十秒—— 是一个作了器官移植的病人，
（录像）路克 马萨拉：“我曾经病得很重，都不能下床。 我没法上学，生活很惨淡。 我不能出门， 课间不能打篮球， 因为每每一回教室 我就感觉要昏倒。 我觉得特别痛苦。 我面临的是基本上终生的洗肾， 简直不能想象 生活会是什么样子。 手术之后， 生活对我变得容易多了。 我能做的事情多了很多。 我能在学校里玩摔跤， 我成了摔跤队长，感觉真棒。 我能够像个正常人一样有朋友， 全是因为医生用了我自身的细胞，给我做了个肾脏。 我的新肾脏将伴随着我。 伴我一生。我别无它求了。”
（掌声）
胡安 安瑞奎兹：这些试验有时还真灵， 灵的时候是很酷的。 路克，请上台来。
（掌声）
路克，直到昨晚 上次你见到安东尼医生是什么时候？
路克：十年前，我做手术的时候—— 能见到他真好。
（笑声）
（掌声）
胡克：和大家讲讲你现在在做什么。
路克：我现在在上大学，在康涅狄格州立大学。 我上二年级，学传媒信息，电视和媒体专业。 我试着过正常人的生活， 这时我长大时一直梦想的。 当时很难做到，因为我生来就有脊柱裂， 我的肾脏和膀胱都不能正常工作。 我做过十六个外科手术， 最后十岁的时候肾脏还是衰竭了， 快要死了。 这个移植手术降临了， 让我成为了今天的我， 救了我。
（掌声）
胡克：安东尼一定做了上百个这样的手术了吧？
路克：据我所知，他在实验室里辛勤工作， 创造了很多新奇古怪的方案。 我知道我是前十个接受这项手术的病人， 那时候我才十岁，我不知道这有多酷。 我只是个孩子。我当时只是： “好吧，又一个手术，我做就是了。” （笑声） 我当时想做的仅仅是活的健康一点， 没有意识到手术的伟大之处，直到我长大了。 现在我明白他做的研究有多么伟大。
胡克：当你突然间接到我们的电话—— 安东尼是很害羞的一个人， 我们很是费了一番唇舌 才得到他这么低调的人的同意， 把路克带到现场来。 路克，当你去你的传媒学教授说—— 传媒学是你的专业—— 当你征得他们的同意来上TED时， 这多少和传媒学有点关系， 他们有什么反应？
路克：大部分人都赞同， 他们说：“照照片回来， 给我网上的录像看。”或者是：“真替你高兴。” 有几个有点保留， 但是我说服了他们， 我都搞定了。
胡克：今天见面真是我的荣幸 谢谢你。（路克：谢谢你们。）
胡克：谢谢你，安东尼医生。
（掌声）


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Anthony Atala: Printing a human kidney
There's actually a major health crisis today in terms of the shortage of organs. The fact is that we're living longer. Medicine has done a much better job of making us live longer. And the problem is, as we age, our organs tend to fail more. And so currently there are not enough organs to go around. In fact, in the last 10 years, the number of patients requiring an organ has doubled, while in the same time, the actual number of transplants has barely gone up. So this is now a public health crisis.

So that's where this field comes in that we call the field of regenerative medicine. It really involves many different areas. You can use, actually, scaffolds, biomaterials -- they're like the piece of your blouse or your shirt -- but specific materials you can actually implant in patients and they will do well and help you regenerate. Or we can use cells alone, either your very own cells or different stem cell populations. Or we can use both; we can use, actually, biomaterials and the cells together. And that's where the field is today.

But it's actually not a new field. Interestingly, this is a book that was published back in 1938. It's titled "The Culture of Organs." The first author, Alexis Carrel, a Nobel Prize winner. He actually devised some of the same technologies used today for suturing blood vessels. And some of the blood vessel grafts we use today were actually designed by Alexis. But I want you to note his co-author: Charles Lindbergh. That's the same Charles Lindbergh who actually spent the rest of his life working with Alexis at the Rockefeller Institute in New York in the area of the culture of organs.

So if the field's been around for so long, why so few clinical advances? And that really has to do to many different challenges. But if I were to point to three challenges, the first one is actually the design of materials that could go in your body and do well over time. And many advances now, we can do that fairly readily. The second challenge was cells. We could not get enough of your cells to grow outside of your body. Over the last 20 years, we've basically tackled that. Many scientists can now grow many different types of cells -- plus we have stem cells. But even now, 2011, there's still certain cells that we just can't grow from the patient. Liver cells, nerve cells, pancreatic cells -- we still can't grow them even today. And the third challenge is vascularity, the actual supply of blood to allow those organs or tissues to survive once we regenerate them.

So we can actually use biomaterials now. This is actually a biomaterial. We can weave them, knit them, or we can make them like you see here. This is actually like a cotton candy machine. You saw the spray going in. That was like the fibers of the cotton candy creating this structure, this tubularized structure, which is a biomaterial that we can then use to help your body regenerate using your very own cells to do so. And that's exactly what we did here.

This is actually a patient who presented with a deceased organ, and we then created one of these smart biomaterials, and then we then used that smart biomaterial to replace and repair that patient's structure. What we did was we actually used the biomaterial as a bridge so that the cells in the organ could walk on that bridge, if you will, and help to bridge the gap to regenerate that tissue. And you see that patient now six months after with an X-ray showing you the regenerated tissue, which is fully regenerated when you analyze it under the microscope. We can also use cells alone. These are actually cells that we obtained. These are stem cells that we create from specific sources, and we can drive them to become heart cells. And they start beating in culture. So they know what to do. The cells genetically know what to do, and they start beating together. Now today, many clinical trials are using different kinds of stem cells for heart disease. So that's actually now in patients.

Or if we're going to use larger structures to replace larger structures, we can then use the patient's own cells, or some cell population, and the biomaterials, the scaffolds, together. So the concept here: so if you do have a deceased or injured organ, we take a very small piece of that tissue, less than half the size of a postage stamp. We then tease the cells apart, we grow the cells outside the body. We then take a scaffold, a biomaterial, again, looks very much like a piece of your blouse or your shirt. We then shape that material, and we then use those cells to code that material one layer at a time -- very much like baking a layer cake, if you will. We then place it in an oven-like device, and we're able to create that structure and bring it out. This is actually a heart valve that we've engineered. And you can see here, we have the structure of the heart valve and we've seeded that with cells, and then we exercise it. So you see the leaflets opening and closing -- of this heart valve that's currently being used experimentally to try to get it to further studies.

Another technology that we have used in patients actually involves bladders. We actually take a very small piece of the bladder from the patient -- less than half the size of a postage stamp. We then grow the cells outside the body, take the scaffold, coat the scaffold with the cells -- the patient's own cells, two different cell types. We then put it in this oven-like device. It has the same conditions as the human body -- 35 degrees centigrade, 95 percent oxygen. A few weeks later, you have your engineered organ that we're able to implant back into the patient. For these specific patients, we actually just suture these materials. We use three-dimensional imagining analysis, but we actually created these biomaterials by hand.

But we now have better ways to create these structures with the cells. We use now some type of technologies, where for solid organs, for example, like the liver, what we do is we take discard livers. As you know, a lot of organs are actually discarded, not used. So we can take these liver structures, which are not going to be used, and we then put them in a washing machine-like structure that will allow the cells to be washed away. Two weeks later, you have something that looks like a liver. You can hold it like a liver, but it has no cells; it's just a skeleton of the liver. And we then can re-perfuse the liver with cells, preserving the blood vessel tree. So we actually perfuse first the blood vessel tree with the patient's own blood vessel cells, and we then infiltrate the parenchyma with the liver cells. And we now have been able just to show the creation of human liver tissue just this past month using this technology.

Another technology that we've used is actually that of printing. This is actually a desktop inkjet printer, but instead of using ink, we're using cells. And you can actually see here the printhead going through and printing this structure, and it takes about 40 minutes to print this structure. And there's a 3D elevator that then actually goes down one layer at a time each time the printhead goes through. And then finally you're able to get that structure out. You can pop that structure out of the printer and implant it. And this is actually a piece of bone that I'm going to show you in this slide that was actually created with a desktop printer and implanted as you see here. That was all new bone that was implanted using these techniques.

Another more advanced technology we're looking at right now, our next generation of technologies, are more sophisticated printers. This particular printer we're designing now is actually one where we print right on the patient. So what you see here -- I know it sounds funny, but that's the way it works. Because in reality, what you want to do is you actually want to have the patient on the bed with the wound, and you have a scanner, basically like a flatbed scanner. That's what you see here on the right side; you see a scanner technology that first scans the wound on the patient and then it comes back with the printheads actually printing the layers that you require on the patients themselves.

This is how it actually works. Here's the scanner going through scanning the wound. Once it's scanned, it sends information in the correct layers of cells where they need to be. And now you're going to see here a demo of this actually being done in a representative wound. And we actually do this with a gel, so that you can lift the gel material. So once those cells are on the patient they will stick where they need to be. And this is actually new technology still under development.

We're also working on more sophisticated printers. Because in reality, our biggest challenge are the solid organs. I don't know if you realize this, but 90 percent of the patients on the transplant list are actually waiting for a kidney. Patients are dying every day because we don't have enough of those organs to go around. So this is more challenging -- large organ, vascular, a lot of blood vessel supply, a lot of cells present. So the strategy here is -- this is actually a CT scan, an X-ray -- and we go layer by layer, using computerized morphometric imaging analysis and 3D reconstruction to get right down to those patient's own kidneys. We then are able to actually image those, do 360 degree rotation to analyze the kidney in its full volumetric characteristics, and we then are able to actually take this information and then scan this in a printing computerized form. So we go layer by layer through the organ, analyzing each layer as we go through the organ. And we then are able to send that information, as you see here, through the computer and actually design the organ for the patient. This actually shows the actual printer. And this actually shows that printing.

In fact, we actually have the printer right here. So while we've been talking today, you can actually see the printer back here in the back stage. That's actually the actual printer right now, and that's been printing this kidney structure that you see here. It takes about seven hours to print a kidney, so this is about three hours into it now. And Dr. Kang's going to walk onstage right now, and we're actually going to show you one of these kidneys that we printed a little bit earlier today. Put on a pair of gloves here. Thank you. Go backwards. So, these gloves are a little bit small on me, but here it is. You can actually see that kidney as it was printed earlier today.

(Applause)

Has a little bit of consistency to it. This is Dr. Kang who's been working with us on this project, and part of our team. Thank you, Dr. Kang. I appreciate it.

(Applause)

So this is actually a new generation. This is actually the printer that you see here onstage. And this is actually a new technology we're working on now. In reality, we now have a long history of doing this. I'm going to share with you a clip in terms of technology we have had in patients now for a while.

And this is actually a very brief clip -- only about 30 seconds -- of a patient who actually received an organ.

(Video) Luke Massella: I was really sick. I could barely get out of bed. I was missing school. It was pretty much miserable. I couldn't go out and play basketball at recess without feeling like I was going to pass out when I got back inside. I felt so sick. I was facing basically a lifetime of dialysis, and I don't even like to think about what my life would be like if I was on that. So after the surgery, life got a lot better for me. I was able to do more things. I was able to wrestle in high school. I became the captain of the team, and that was great. I was able to be a normal kid with my friends. And because they used my own cells to build this bladder, it's going to be with me. I've got it for life, so I'm all set.

(Applause)

Juan Enriquez: These experiments sometimes work, and it's very cool when they do. Luke, come up please.

(Applause)

So Luke, before last night, when's the last time you saw Tony?

LM: 10 years ago, when I had my surgery -- and it's really great to see him.

(Laughter)

(Applause)

JE: And tell us a little bit about what you're doing.

LM: Well right now I'm in college at the University of Connecticut. I'm a sophomore and studying communications, TV and mass media. And basically trying to live life like a normal kid, which I always wanted growing up. But it was hard to do that when I was born with spina bifida and my kidneys and bladder weren't working. I went through about 16 surgeries, and it seemed impossible to do that when I was in kidney failure when I was 10. And this surgery came along and basically made me who I am today and saved my life.

(Applause)

JE: And Tony's done hundreds of these?

LM: What I know from, he's working really hard in his lab and coming up with crazy stuff. I know I was one of the first 10 people to have this surgery. And when I was 10, I didn't realize how amazing it was. I was a little kid, and I was like, "Yeah. I'll have that. I'll have that surgery." (Laughter) All I wanted to do was to get better, and I didn't realize how amazing it was until now that I'm older and I see the amazing things that he's doing.

JE: When you got this call out of the blue -- Tony's really shy, and it took a lot of convincing to get somebody as modest as Tony to allow us to bring Luke. So Luke, you go to your communications professors -- you're majoring in communications -- and you ask them for permission to come to TED, which might have a little bit to do with communications, and what was their reaction?

LM: Most of my professors were all for it, and they said, "Bring pictures and show me the clips online," and "I'm happy for you." There were a couple that were a little stubborn, but I had to talk to them. I pulled them aside.

JE: Well, it's an honor and a privilege to meet you. Thank you so much. (LM: Thank you so much.)

JE: Thank you, Tony.

(Applause)