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无需移植心脏 神奇“心脏补丁”也能救命

更新时间:2018-3-18 9:47:02 来源:纽约时报中文网 作者:佚名

Can we bring hearts back from the dead?
无需移植心脏 神奇“心脏补丁”也能救命

Surgeons like to say that when someone suffers a heart attack, time is muscle. The heart depends on a continuous supply of oxygen from the coronary arteries; if these become blocked and that supply stops, the heart’s muscle cells start to die off within just a few minutes. In many cases, unless surgeons can relieve the blockage within the hour, more than 1 billion muscle cells are irreversibly lost.

外科医生喜欢说这样一句话:对于遭遇心脏骤停的患者,时间就是生命。心脏依赖于冠状动脉持续不断输送的氧气才能存活,如果血氧供应遭到阻塞,心肌细胞就会在短短几分钟之内开始死亡。一般而言,除非医生能在一小时之内消除血管阻塞,否则将会有多达10亿个心肌细胞不可逆转地凋亡。

Those who survive are often left with permanent heart failure – a group which includes approximately 450,000 people in the UK. Within the five years following an attack, 50% of them will no longer be alive. “Eventually their hearts become so weak that they can’t sustain sufficient blood flow and they just stop altogether,” says Sanjay Sinha, a cardiologist at Addenbrooke’s Hospital, Cambridge.

侥幸经历心脏停搏而不死的幸运患者也会出现永久性心力衰竭。单在英国,心力衰竭患者就有45万人之多。然而,心脏停搏后5年生存率却只有50%。"他们的心脏功能非常衰弱,无力承受足够的血流量,最终以停止跳动而告终,"剑桥阿登布鲁克医院(Addenbrooke's Hospital)心脏病专家桑杰·辛哈(Sanjay Sinha)表示。

But even within the next five years, regenerative medicine may provide a radical new alternative: growing live, beating ‘heart patches’.

然而在未来五年内,再生性疗法将提供另一种可能:那就是培育鲜活而不断跳动的"心脏补丁"。

The challenge is that unlike some of our other organs, like the skin and liver, the heart has a very limited ability to self-heal. Heart muscle cells replicate at a rate of just 0.5% a year, not sufficient to repair any significant damage. Instead, the dead cells are replaced by thick layers of tough, rigid scar tissue, meaning that sections of the heart simply cease to function.

与皮肤、肝脏等其他器官相比,心脏的自我修复能力很差。心肌细胞每年的复制率只有0.5%,无力修复重大损伤。另外,心肌细胞死亡后,会被无生命力的僵硬疤痕组织所取代,意味着这部分心脏永久性地失去了功能。

At the moment, the only medical option for patients with heart failure is a heart transplant. But a lack of donor organs means that just 200 of these operations can be performed in the UK each year. “I don’t think we could ever get the number of donors we need because you don’t get thousands of young people dying with healthy hearts,” says Sinha. “There’s only a very small pool of people who’ve died, in traffic accidents or through head injuries, where the heart is still strong and can be used for a transplant.”

目前,解决心力衰竭问题的唯一医学手段是心脏移植。但是由于供体有限,英国每年只能做200例心脏移植手术。"每年,心脏健康的年轻人意外死亡的案例十分有限,因此我认为我们永远不会有足够多的供体,"辛哈说。"每年只有为数很少的心脏强健,适合移植的年轻人因为交通事故或者脑部外伤而死亡。"

Stem cell medicine may provide an alternative. In clinical trials, scientists have attempted to remuscularise damaged hearts by injecting individual stem cells – which can develop into many different types – from the patient’s blood or bone marrow directly into the heart.

另一个有希望的疗法是干细胞医学。在临床试验里,科学家正在研究能否通过直接向心脏注射心肌性干细胞(干细胞可以通过诱导发育为各种人体细胞)而让破损心脏重新肌组织化,干细胞的来源是患者的血液或骨髓。

While these approaches have successfully regenerated damaged blood vessels and thus improved blood flow to the heart, they have shown minimal benefit in terms of solving the major problem – growing back lost heart muscle. This is thought to be because 95% of the injected stem cells fail to attach to the heart and are immediately lost into the bloodstream.

尽管这一疗法已经成功再生了受损血管并促进了血液向心脏的回流,但是由于没能解决主要问题(即,让坏死的心肌细胞重新生长),因此它们对病人的收益非常有限。在注入心脏的干细胞中,有95%没能附着到心脏上,而是立刻被血流冲走。

But along with a team of stem cell biologists at the University of Cambridge’s Stem Cell Institute, Sinha is working on a slightly different idea: heart patches.

为此,辛哈正在和剑桥大学干细胞学院的干细胞生物学研究小组一道共同研究另一种疗法:心脏补丁。

These tiny, beating pieces of heart muscle, each less than 2.5 sq centimetres (0.5 square inches) in area and half a centimetre thick, are made in small dishes in the lab. Grown over the course of a month, the patches are made by taking blood cells and reprogramming them into a particular form of stem cell which can be converted into any cell in the human body – in this case heart muscle cells, blood vessel cells, and the epicardium, the membrane around the heart which gives it its shape. These clusters of heart cells are then grown in a special scaffold which organises and aligns them into a formation resembling real heart tissue.

这种不断跳动的心肌组织只有2.5平方厘米大小,5毫米厚,在实验室的小型培养皿中培育而成。心肌补丁是通过对血细胞重新编程,使之先转化为一种特殊干细胞,再转化成人体任意一种细胞(例如心肌细胞、血管细胞和构成心脏外形的心外膜),然后生长一个月后而形成。科学家把单个心肌细胞放入一种特殊框架进行培育,最终生长成为真实心肌组织的外形。

“We believe that these patches will stand a much greater chance of being naturally assimilated into a patient’s heart, as we’re creating fully functional tissue which already beats and contracts through combining all these different cell types which communicate with each other,” Sinha says.

"我们相信,心脏补丁有很大希望能够与患者心脏实现自然融合。通过把不同种类的细胞组合在一起,让它们彼此沟通,我们已经制作出了能够跳动和收缩,具备完全功能的心肌组织,"辛哈表示。

“We know the epicardium cells are particularly important in co-ordinating proper development of heart muscle because research has shown that in developing embryos, there’s a lot of crosstalk which occurs between the epicardium and the developing heart.”

"研究发现,胚胎发育过程中,心外膜和心脏之间会产生大量互动,因此心外膜细胞对于心肌细胞的协调发育具有重要的作用。"

Sinha is currently preparing to trial the patches, first in mice and then pigs. If all goes to plan, in five years he may be ready to conduct a first human trial.

辛哈目前正在计划开展心脏补丁临床试验,首先做小鼠和猪的动物实验。如果一切顺利,将在5年内开展第一例人体试验。

On beat

持续跳动

He’s not alone. In the US, a collaborative team of scientists from Stanford University, Duke University and the University of Wisconsin are also trying to build heart patches.

他并不孤单。一个由斯坦福大学(Stanford University)、杜克大学(Duke University)和威斯康辛大学(University of Wisconsin)组成的联合研发小组也正在开发心脏补丁。

Like Sinha, they envisage a future procedure where a combination of ultrasound and MRI scans are used to locate the scarred structures in the heart. Based on the shape of the scarring, they’d then 3D print a custom heart patch of any shape or dimension. Surgeons would open up the chest cavity and stitch the patch directly to the heart in a way that links it up with the existing veins and arteries.

和辛哈一样,他们也正在计划使用超声波和MRI扫描定位心脏受损部位。根据损伤的形状,他们将用3D打印机定制一块任意大小和形状的心脏补丁。然后,外科医生将打开患者胸腔把补丁直接缝补到心脏上去,并连接现有静脉和动脉。

“For patients with particularly severe heart failure, multiple patches will be required in multiple places as the whole heart dilates to try to adapt to the damage,” says University of Wisconsin regenerative biology professor Tim Kamp, who is part of the collaboration. “It changes shape from being like a rugby ball to a big balloon or basketball.”

"心力严重衰竭的病人会出现心脏膨大以适应损伤,在此情况下需要在不同部位修补好几块补丁,"合作研究计划成员、威斯康辛大学再生生物学教授蒂姆·卡姆(Tim Kamp)说。"就像曲棍球膨大成为一只大气球或者篮球那样。"

One of the main challenges with this approach is how to electrically integrate the new patch with the heart to ensure that both beat in synchrony. Any defective electrical connections could stimulate an abnormal heart rhythm.

这种新疗法的主要挑战在于,如何通过让新补丁和心脏实现电信号融合,从而让二者能够同时跳动。任何存在缺陷的电信号传导都会导致出现异常心率。

“We can put the patch on the heart with our surgical tools but we can’t force them to shake hands,” Kamp says. “But we hope they will. We anticipate that the electrical signals which pass through the heart muscle like a wave and tell it to contract will drive the new patch to contract at the same rate.”

"我们能通过外科器械把补丁缝到心脏上去,但不能强迫它们协调行动,"卡姆说。"但是我们希望它们能这样。我们认为,像电波一样通过心肌,向其发布收缩命令的电信号也能让新补丁以同样幅度收缩。"

If these challenges can be overcome, Sinha believes they could save not only lives, but dollars.

辛哈说,如果能够攻克这一难关,心脏补丁技术就不仅能够拯救无数生命,还能节约大笔资金。

In the UK, heart transplant procedures cost around £500,000 ($690,000) including inpatient care. But for the thousands of heart failure patients who are not able to get a transplant, the cost implications of continuous medical care and repeated hospital admissions can be even bigger. By contrast, current estimates place the potential cost of a heart patch treatment at around £70,000 ($96,000).

在英国,心脏移植手术费用大约是50万英镑(69万美元),包括住院费用。但是对于无法接受移植的成千上万心力衰竭患者,持续性长期治疗和定期住院的费用更加高昂。比较而言,当前心脏补丁疗法的费用只需7万英镑(9.6万美元)左右。

In addition, because the patches are made using their own blood, patients undergoing the procedure would not have to undergo some of the complications associated with heart transplants – like high doses of immunosuppressant drugs. “An injured heart is a highly inflamed, hostile environment which can be difficult for new tissue to survive in,” Kamp says. “The advantage of these heart patches is that they’re personalised to the patient, so the heart is unlikely to reject them.”

另外,由于心脏补丁是由患者自身的血液细胞为原料制成,接受心脏补丁治疗的患者无需承受心脏移植手术并发症带来的痛苦,例如长期服用免疫抑制药物。"一个受伤的心脏是一个充满敌意的环境,新组织很难存活,"卡姆说,"心脏补丁的优势在于,它是为患者定制的,因此心脏不会排斥补丁组织。"

The technology could change the lives of millions around the world, the researchers say.

研究者说,新技术将改变全球以百万计的患者的人生。

“Heart failure can pretty much incapacitate people,” says Sinha. “You’re constantly exhausted, you can’t even climb a flight of stairs. But for the first time, we think we’re actually able to recreate real living heart tissue, which is identical to that of the patient, where the cells are talking to each other in mysterious and wonderful ways and working together as they do in the body.

"心力衰竭会让很多患者生存质量低劣,"辛哈表示。"你很容易感到精疲力竭,甚至没法爬上客机舷梯。但是我们现在已经能够制造鲜活的心脏组织,并让它和患者之间完全没有排斥反应。补丁细胞和原有心脏细胞将以神秘而奇妙的方式互相对话,共同协作。"

“If we can fine-tune it in the next few years, and make sure it’s completely safe, then it could help these people live a normal life again.”

"未来几年内,如果我们能进行更加细致的研究,并且证实心脏补丁具有绝对安全性,我们就能帮助成千上万的心脏病患者重新获得美好的人生。"

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