Can we regenerate heart muscle with stem cells? | Chuck Murry

翻译人员: Lipeng Chen 校对人员: Tianji (Homer) Li

I'd like to tell you about a patient named Donna.

我想和你们讲讲一个 叫唐娜的病人。

In this photograph, Donna was in her mid-70s,

在这张照片中，唐娜70多岁，

a vigorous, healthy woman,

一个精力充沛、健康的女人，

the matriarch of a large clan.

也是一个大家族的领袖。

She had a family history of heart disease, however,

但她有心脏病家族史，

and one day, she had the sudden onset of crushing chest pain.

有一天，她突然感到胸痛。

Now unfortunately, rather than seeking medical attention,

不幸的是，唐娜没有 寻求医疗救助，

Donna took to her bed for about 12 hours until the pain passed.

而是在床上躺了大约12个小时， 直到疼痛过去。

The next time she went to see her physician,

下次她去看医生时，

he performed an electrocardiogram,

医生做了心电图，

and this showed that she'd had a large heart attack,

这表明她心脏病发了，

or a "myocardial infarction" in medical parlance.

或者医学术语中的“心肌梗塞”。

After this heart attack, Donna was never quite the same.

在这次心脏病发作之后， 唐娜就再也不一样了。

Her energy levels progressively waned,

她的体能逐渐下降，

she couldn't do a lot of the physical activities she'd previously enjoyed.

她不能做很多以前 喜欢的体育活动。

It got to the point where she couldn't keep up with her grandkids,

逐渐到了她不能跟上 孙子孙女的地步，

and it was even too much work to go out to the end of the driveway

而且要走到楼道尽头 去拿邮件也变得费劲了。

to pick up the mail.

One day, her granddaughter came by to walk the dog,

一天，她的孙女过来遛狗，

and she found her grandmother dead in the chair.

她发现奶奶死在椅子上。

Doctors said it was a cardiac arrhythmia that was secondary to heart failure.

医生说这是一种 继发于心力衰竭的心律失常。

But the last thing that I should tell you

但我最后要告诉你们的是

is that Donna was not just an ordinary patient.

唐娜不仅仅是个普通病人。

Donna was my mother.

唐娜是我母亲。

Stories like ours are, unfortunately, far too common.

不幸的是，像我们 这样的故事太普遍了。

Heart disease is the number one killer in the entire world.

心脏病是全世界头号杀手。

In the United States,

在美国，

it's the most common reason patients are admitted to the hospital,

这是病人入院的最常见原因，

and it's our number one health care expense.

这是我们最大的医疗费用。

We spend over a 100 billion dollars -- billion with a "B" --

我们花了1000多亿美元—— 1000多亿美元——

in this country every year

在这个国家每年

on the treatment of heart disease.

用于心脏病的治疗。

Just for reference, that's more than twice the annual budget

顺便说下，这是 华盛顿州年度预算的

of the state of Washington.

两倍多。

What makes this disease so deadly?

是什么使这种疾病如此致命？

Well, it all starts with the fact that the heart is the least regenerative organ

这一切都是因为心脏是在人体内

in the human body.

再生能力最小的器官。

Now, a heart attack happens when a blood clot forms in a coronary artery

当将血液注入心脏壁的 冠状动脉中形成血液凝块时，

that feeds blood to the wall of the heart.

心脏病就会发作。

This plugs the blood flow,

这会堵塞血流，

and the heart muscle is very metabolically active,

心脏肌肉的新陈代谢非常活跃，

and so it dies very quickly,

所以在血液流动

within just a few hours of having its blood flow interrupted.

中断后的几个小时内， 心脏很快就死了。

Since the heart can't grow back new muscle,

因为心脏不能长出新的心肌，

it heals by scar formation.

它通过形成疤痕而愈合。

This leaves the patient with a deficit

这使病人在

in the amount of heart muscle that they have.

心肌数量上形成了短缺。

And in too many people, their illness progresses to the point

在太多的人身上， 他们的病情已经坏到

where the heart can no longer keep up with the body's demand for blood flow.

心脏无法满足身体对 血液流动的需求。

This imbalance between supply and demand is the crux of heart failure.

供求失衡是心力衰竭的 症结所在。

So when I talk to people about this problem,

所以当我和人们 谈论这个问题时，

I often get a shrug and a statement to the effect of,

我经常会耸耸肩， 然后说一句话，

"Well, you know, Chuck, we've got to die of something."

“好吧，你知道，查克， 我们总会为某件事而死。”

(Laughter)

（笑声）

And yeah, but what this also tells me

是的，但这也告诉了我

is that we've resigned ourselves to this as the status quo because we have to.

我们已经对这个 现状自我放弃了。

Or do we?

真是这样吗？

I think there's a better way,

我觉得有更好的方法，

and this better way involves the use of stem cells as medicines.

这种更好的方法包括 使用干细胞作为药物。

So what, exactly, are stem cells?

那么，究竟什么是干细胞？

If you look at them under the microscope, there's not much going on.

如果你在显微镜下 观察它们，太简单了。

They're just simple little round cells.

它们只是简单的小圆形细胞。

But that belies two remarkable attributes.

但这掩盖了两个显著的特征。

The first is they can divide like crazy.

首先，它们可以疯狂地分裂。

So I can take a single cell, and in a month's time,

所以我只需要一个 细胞，一个月后，

I can grow this up to billions of cells.

我可以把它长到数十亿个细胞。

The second is they can differentiate or become more specialized,

第二，它们可以分化或 变得更具指向性，

so these simple little round cells can turn into skin, can turn into brain,

所以这些简单的圆形细胞 可以变成皮肤，可以变成大脑，

can turn into kidney and so forth.

可以变成肾脏等等。

Now, some tissues in our bodies are chock-full of stem cells.

现在，我们体内的一些 组织充满了干细胞。

Our bone marrow, for example, cranks out billions of blood cells every day.

例如，我们的骨髓每天 产生数十亿个血细胞。

Other tissues like the heart are quite stable,

心脏等其他组织相当稳定，

and as far as we can tell, the heart lacks stem cells entirely.

据我们所知，心脏 完全缺乏干细胞。

So for the heart, we're going to have to bring stem cells in from the outside,

所以对于心脏来说， 我们必须从外部引进干细胞，

and for this, we turn to the most potent stem cell type,

为此，我们转向最 有效的干细胞类型，

the pluripotent stem cell.

多能干细胞。

Pluripotent stem cells are so named

多能干细胞就是这样命名的，

because they can turn into any of the 240-some cell types

因为它们可以变成构成人体的 240种细胞类型中的

that make up the human body.

任何一种。

So this is my big idea:

这是我的想法：

I want to take human pluripotent stem cells,

我想培养人类多能干细胞，

grow them up in large numbers,

让它们大量分裂，

differentiate them into cardiac muscle cells

进而分化为心肌细胞，

and then take them out of the dish

然后把它们从培养皿中拿出来，

and transplant them into the hearts of patients who have had heart attacks.

再把它们移植到 心脏病患者的心脏上。

I think this is going to reseed the wall with new muscle tissue,

我认为新的心肌细胞会 缝合心脏上的伤口，

and this will restore contractile function to the heart.

进而会恢复心脏的收缩功能。

(Applause)

（掌声，欢呼）

Now, before you applaud too much, this was my idea 20 years ago.

在你们鼓太多掌之前， 我想说这是我20年前的想法。

(Laughter)

（笑声）

And I was young, I was full of it, and I thought,

我很年轻，我充满了 这种想法，我想，

five years in the lab, and we'll crank this out,

在实验室里呆五年， 我们会解决这个问题的，

and we'll have this into the clinic.

我们会把这个想法 在临床上变成现实。

Let me tell you what really happened.

我来告诉你们到底发生了什么。

(Laughter)

（笑声）

We began with the quest to turn these pluripotent stem cells into heart muscle.

我们开始探索将这些 多能干细胞转化为心肌细胞。

And our first experiments worked, sort of.

我们的第一个实验 差不多算成功了。

We got these little clumps of beating human heart muscle in the dish,

我们在培养皿中放了 一些跳动的人体心脏肌肉，

and that was cool, because it said, in principle,

这很酷，因为它表明，原则上

this should be able to be done.

我的想法应该可以做到。

But when we got around to doing the cell counts,

但当我们开始做细胞计数时，

we found that only one out of 1,000 of our stem cells

我们发现1000个 干细胞中只有一个

were actually turning into heart muscle.

实际上变成了心肌细胞。

The rest was just a gemisch of brain and skin and cartilage

其余的只是大脑细胞、皮肤细胞、 软骨细胞和肠道细胞的混合。

and intestine.

So how do you coax a cell that can become anything

那么你如何让一个能 变成任何东西的细胞

into becoming just a heart muscle cell?

只变成心肌细胞呢？

Well, for this we turned to the world of embryology.

为了这个，我们转向 胚胎学的世界。

For over a century, the embryologists had been pondering

一个多世纪以来， 胚胎学家一直在思考

the mysteries of heart development.

心脏发育的奥秘。

And they had given us what was essentially a Google Map

他们给了我们一张 类似谷歌地图的东西，

for how to go from a single fertilized egg

这指示如何从一个受精卵

all the way over to a human cardiovascular system.

一直发展到人类心血管系统。

So we shamelessly absconded all of this information

所以我们贪婪地 使用了所有这些信息，

and tried to make human cardiovascular development happen in a dish.

并试图使人的心血管发育 发生在一个培养皿里。

It took us about five years, but nowadays,

我们花了五年时间，但现在，

we can get 90 percent of our stem cells to turn into cardiac muscle --

我们可以让90%的干细胞 变成心肌细胞——

a 900-fold improvement.

提高了900倍。

So this was quite exciting.

所以这很令人兴奋。

This slide shows you our current cellular product.

这张幻灯片向你们展示 我们当前的细胞产物。

We grow our heart muscle cells in little three-dimensional clumps

我们的心肌细胞在 被称为心脏类器官的

called cardiac organoids.

三维结构中发育。

Each of them has 500 to 1,000 heart muscle cells in it.

它们每个都有500到 1000个心肌细胞。

If you look closely, you can see these little organoids are actually twitching;

如果你仔细观察，你会发现 这些小的类器官实际上在运动；

each one is beating independently.

每个类器官都在独立地跳动。

But they've got another trick up their sleeve.

但它们还有另一个小奥秘。

We took a gene from jellyfish that live in the Pacific Northwest,

我们从太平洋西北部的水母身上 提取了一个基因，

and we used a technique called genome editing

我们使用了一种叫做 基因组编辑的技术

to splice this gene into the stem cells.

把这个基因拼接到干细胞中。

And this makes our heart muscle cells flash green every time they beat.

这使得我们的心肌细胞 每跳动一次都会闪烁绿色。

OK, so now we were finally ready to begin animal experiments.

现在，我们终于准备好 开始动物实验了。

We took our cardiac muscle cells

我们取了我们的心肌细胞，

and we transplanted them into the hearts of rats

把它们移植到有 实验性心脏病发作的

that had been given experimental heart attacks.

老鼠的心脏里。

A month later, I peered anxiously down through my microscope

一个月后，我焦急地 透过显微镜观察，

to see what we had grown,

看看我们长出了什么，

and I saw ...

我看到…

nothing.

没有什么。

Everything had died.

一切都死了。

But we persevered on this, and we came up with a biochemical cocktail

但我们坚持不懈， 想出了一种生化鸡尾酒，

that we called our "pro-survival cocktail,"

我们称之为“助生鸡尾酒”，

and this was enough to allow our cells to survive

这足以通过移植的压力，

through the stressful process of transplantation.

让我们的细胞存活下来。

And now when I looked through the microscope,

现在当我通过显微镜看的时候，

I could see this fresh, young, human heart muscle

我能看到这些新鲜的、 年轻的人类心肌

growing back in the injured wall of this rat's heart.

在受伤的老鼠心脏壁上生长。

So this was getting quite exciting.

这变得非常令人兴奋。

The next question was:

下一个问题是：

Will this new muscle beat in synchrony with the rest of the heart?

这种新的肌肉会与心脏的 其他部分同步跳动吗？

So to answer that,

要回答这个问题，

we returned to the cells that had that jellyfish gene in them.

我们回到了含有 水母基因的细胞。

We used these cells essentially like a space probe

我们基本上就把这些细胞 当做太空探测器一样来使用，

that we could launch into a foreign environment

我们把它们放到一个 陌生的环境中，

and then have that flashing report back to us

然后我们通过返还给 我们的闪烁信号，

about their biological activity.

来了解它们的生物活性。

What you're seeing here is a zoomed-in view,

你们现在看到的是一个放大的

a black-and-white image of a guinea pig's heart

豚鼠心脏的黑白图像，

that was injured and then received three grafts of our human cardiac muscle.

这颗心脏受了伤， 然后接受了三轮的人体心肌移植。

So you see those sort of diagonally running white lines.

你们可以看到那些斜行的白线。

Each of those is a needle track

每个都是针线，

that contains a couple of million human cardiac muscle cells in it.

里面有几百万人类心肌细胞。

And when I start the video, you can see what we saw

当我开始放视频的时候， 你们就可以看到我们透过显微镜时

when we looked through the microscope.

看到的景象。

Our cells are flashing,

细胞在闪烁，

and they're flashing in synchrony,

而且它们在同步闪烁，

back through the walls of the injured heart.

透过受伤的心脏壁传回来。

What does this mean?

这是什么意思？

It means the cells are alive,

这意味着细胞是活的，

they're well, they're beating,

它们很好，它们在跳动，

and they've managed to connect with one another

它们已经成功的融为一体了，

so that they're beating in synchrony.

所以它们在同步跳动。

But it gets even more interesting than this.

但还有更有意思的事情。

If you look at that tracing that's along the bottom,

如果你看底部的线条，

that's the electrocardiogram from the guinea pig's own heart.

这是豚鼠心脏的心电图。

And if you line up the flashing with the heartbeat

如果你把闪光和心跳排成一行

that's shown on the bottom,

如图所示，

what you can see is there's a perfect one-to-one correspondence.

你看到的是一对一的完美对应。

In other words, the guinea pig's natural pacemaker is calling the shots,

换言之，豚鼠自身的 心脏正在主导，

and the human heart muscle cells are following in lockstep

而人体心肌细胞则是 亦步亦趋的跟随着，

like good soldiers.

就像好士兵一样。

(Applause)

（掌声，欢呼）

Our current studies have moved into what I think is going to be

我们目前的研究已经 进入了我所认为的

the best possible predictor of a human patient,

和人类最相近的动物实验阶段，

and that's into macaque monkeys.

那就是猕猴实验。

This next slide shows you a microscopic image

下一张幻灯片是一幅显微图像，

from the heart of a macaque that was given an experimental heart attack

展示了一只实验性心脏病 发作的猕猴心脏，

and then treated with a saline injection.

然后被注射了盐水。

This is essentially like a placebo treatment

这基本上就像安慰剂治疗，

to show the natural history of the disease.

显示疾病的自然发生过程。

The macaque heart muscle is shown in red,

猕猴的心肌呈红色，

and in blue, you see the scar tissue that results from the heart attack.

蓝色部分，你可以看到 心脏病引起的疤痕组织。

So as you look as this, you can see how there's a big deficiency in the muscle

当你看着这张图时， 你会发现心室壁的一部分

in part of the wall of the heart.

肌肉有很大的缺陷。

And it's not hard to imagine how this heart would have a tough time

不难想象这颗心脏在起搏时

generating much force.

会有多么大的阻碍。

Now in contrast, this is one of the stem-cell-treated hearts.

相反，这是颗接受 干细胞治疗的心脏。

Again, you can see the monkey's heart muscle in red,

同样的，你可以看到 猴子的心肌是红色的，

but it's very hard to even see the blue scar tissue,

但是很难看到蓝色的疤痕组织，

and that's because we've been able to repopulate it

那是因为我们用了人类的心肌

with the human heart muscle,

去恢复了它，

and so we've got this nice, plump wall.

所以我们重新有了一扇 漂亮丰满的心室壁。

OK, let's just take a second and recap.

好吧，让我们花点 时间回顾一下。

I've showed you that we can take our stem cells

我已经向你展示了 我们的干细胞

and differentiate them into cardiac muscle.

以及它们分化成心肌细胞的过程。

We've learned how to keep them alive after transplantation,

我们已经学会了如何在 移植后保持它们的活力，

we've showed that they beat in synchrony with the rest of the heart,

我们已经证明它们与心脏的 其他部分同步跳动，

and we've shown that we can scale them up

我们已经证明我们可以在

into an animal that is the best possible predictor of a human's response.

成为最能预测人类反应的 动物身上进行实验。

You'd think that we hit all the roadblocks that lay in our path, right?

你们会认为我们清除了 所有阻碍我们前进的路障，对吧？

Turns out, not.

事实证明，不是这样。

These macaque studies also taught us

这些猕猴的研究也教会了我们

that our human heart muscle cells created a period of electrical instability.

我们人类的心肌细胞造成了 一段时间的心电不稳。

They caused ventricular arrhythmias, or irregular heartbeats,

它们引起了室性心律失常 或不规则的心跳，

for several weeks after we transplanted them.

长达移植后几个星期之久。

This was quite unexpected, because we hadn't seen this in smaller animals.

这完全出乎意料，因为我们 在小动物身上没有看到过。

We've studied it extensively,

我们对这进行了广泛的研究，

and it turns out that it results from the fact that our cellular graphs

结果发现，发生的原因是 我们的细胞图

are quite immature,

很不成熟，

and immature heart muscle cells all act like pacemakers.

未成熟的心肌细胞都像起搏器。

So what happens is, we put them into the heart,

所以当我们把它们放进心脏，

and there starts to be a competition with the heart's natural pacemaker

它们便开始与心脏的 自然起搏竞争

over who gets to call the shots.

决定谁来占主导地位。

It would be sort of like

这就有点像

if you brought a whole gaggle of teenagers into your orderly household all at once,

如果你一下子把一群傻乎乎的青少年 带到你井然有序的家里，

and they don't want to follow the rules and the rhythms of the way you run things,

他们不想遵守你的规则和节奏，

and it takes a while to rein everybody in

需要一段时间来控制所有人，

and get people working in a coordinated fashion.

让人们以协调一致的方式工作。

So our plans at the moment

所以我们现在的计划

are to make the cells go through this troubled adolescence period

是当细胞还在培养皿里的时候，

while they're still in the dish,

让它们经历这个麻烦的“青春期”，

and then we'll transplant them in in the post-adolescent phase,

然后我们在“青春期”后移植它们，

where they should be much more orderly

那时它们会更加的有序，

and be ready to listen to their marching orders.

准备好遵守它们的行军命令。

In the meantime, it turns out we can actually do quite well

同时，事实证明当这种方法和 抗心律失常药物结合时，

by treating with anti-arrhythmia drugs as well.

我们做的相当不错。

So one big question still remains,

还有一个大问题，

and that is, of course, the whole purpose that we set out to do this:

当然，这就是我们开始 做这件事的全部目的：

Can we actually restore function to the injured heart?

我们真的能恢复 受伤心脏的功能吗？

To answer this question,

要回答这个问题，

we went to something that's called "left ventricular ejection fraction."

我们研究了所谓的 “左心室射出分率”。

Ejection fraction is simply the amount of blood

射出分率是每一次起搏时

that is squeezed out of the chamber of the heart

从心腔中挤出来的

with each beat.

血液量。

Now, in healthy macaques, like in healthy people,

健康的猕猴，就像健康人一样，

ejection fractions are about 65 percent.

射出分率约为65%。

After a heart attack, ejection fraction drops down to about 40 percent,

心脏病发作后，射出分率 下降到40%左右，

so these animals are well on their way to heart failure.

所以这些动物很快 就会患上心力衰竭。

In the animals that receive a placebo injection,

在接受安慰剂注射的动物中，

when we scan them a month later,

一个月后当我们扫描它们时，

we see that ejection fraction is unchanged,

我们看到射出分率不变，

because the heart, of course, doesn't spontaneously recover.

因为心脏不会自动恢复。

But in every one of the animals that received a graft

但是在每只接受人体 心肌细胞移植的

of human cardiac muscle cells,

动物身上，

we see a substantial improvement in cardiac function.

我们看到心脏功能 有了实质性的改善。

This averaged eight points, so from 40 to 48 percent.

从40%到48%，平均 有8个点的提升。

What I can tell you is that eight points is better

我能告诉你的是8个点

than anything that's on the market right now

比现在市场上的任何

for treating patients with heart attacks.

用于治疗心脏病患者的东西都要好。

It's better than everything we have put together.

这和我们把所有的东西 放在一起比都要好。

So if we could do eight points in the clinic,

如果我们能在临床上达到8个点，

I think this would be a big deal that would make a large impact

我认为这将会对人类健康

on human health.

会产生很大的影响。

But it gets more exciting.

但是还有更令人兴奋的。

That was just four weeks after transplantation.

这只是移植后的四周。

If we extend these studies out to three months,

如果我们把这些 研究延长到三个月，

we get a full 22-point gain in ejection fraction.

射出分率会增长22个点。

(Applause)

（掌声）

Function in these treated hearts is so good

这些治疗过的心脏功能很好

that if we didn't know up front that these animals had had a heart attack,

以至于如果我们事先不知道 这些动物有过心脏病发作，

we would never be able to tell from their functional studies.

我们永远无法 从功能研究中将它们辨别出来。

Going forward, our plan is to start phase one,

接下来，我们的计划 是开始第一阶段，

first in human trials here at the University of Washington in 2020 --

2020年首次在华盛顿大学 进行人体试验——

two short years from now.

两年后。

Presuming these studies are safe and effective,

假设这些研究是安全有效的，

which I think they're going to be,

我觉得它们是这样的，

our plan is to scale this up and ship these cells all around the world

我们的计划是扩大规模， 把这些细胞运到世界各地

for the treatment of patients with heart disease.

用于治疗心脏病患者。

Given the global burden of this illness,

鉴于这种疾病的全球性负担，

I could easily imagine this treating a million or more patients a year.

我可以很容易地想象， 每年治疗一百万或更多的病人。

So I envision a time, maybe a decade from now,

我设想一个时间，也许十年后，

where a patient like my mother will have actual treatments

像我母亲这样的病人 会接受真正的治疗，

that can address the root cause and not just manage her symptoms.

这可以解决根本原因， 而不仅仅是缓解她的症状。

This all comes from the fact that stem cells give us the ability

这些都因为干细胞让我们有能力

to repair the human body

可以从人类身体的组成部分

from its component parts.

来修复自身。

In the not-too-distant future,

在不久的将来，

repairing humans is going to go

修复人类就要

from something that is far-fetched science fiction

从牵强附会的科幻小说中

into common medical practice.

走进普通的医学实践。

And when this happens,

当这发生时，

it's going to have a transformational effect

它会产生一个颠覆性的效果，

that rivals the development of vaccinations and antibiotics.

可以比肩疫苗和 抗生素的发展。

Thank you for your attention.

谢谢你们的聆听。

(Applause)

（掌声，欢呼）