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在动物组织上生长出的人类肌肉

Human Muscle, Regrown on Animal Scaffolding
在动物组织上生长出的人类肌肉

PITTSBURGH — In the months after a roadside bomb in Afghanistan blew off part of his left thigh, Sgt. Ron Strang wondered if he would ever be able to walk normally again.

匹兹堡——阿富汗路边的炸弹炸掉了罗恩·斯特朗(Ron Strang)中士左腿的部分肌肉,在那之后的几个月,他怀疑这辈子自己能否再次正常行走。

The explosion and subsequent rounds of surgery left Sergeant Strang, 28, a Marine, with a huge divot in his upper thigh where the quadriceps muscle had been. He could move the leg backward, but with so much of the muscle gone he could not kick it forward. He could walk, but only awkwardly.

爆炸和连续数次的手术,在28岁的海军陆战队员斯特朗中士的大腿的四头肌上留下了一道巨大的伤口。由于失去大量的肌肉组织,他的腿只能向后移动,不能向前踢。他可以行走,但动作很笨拙。

“I got really good at falling,” he said of his efforts. And Sergeant Strang, a tall, athletic man, had to give up running.

“我那时练得特别擅长卧倒,”他谈到了自己历经的艰辛。罗恩·斯特朗中士身材高大健硕,他不得不放弃跑步。
 

罗恩·斯特朗与女友莫妮卡·米奇娜(Monica Michna)一起锻炼。他在阿富汗服役时,左腿四头肌部分被炸弹炸飞。

But that was two years ago. Now he walks easily, can run on a treadmill and is thinking of a post-military career as a police officer. “If you know me, or know to look for it, you can see a slight limp,” he said. “But everybody else, they go, ‘I would never have guessed.’ ”

但是那是两年前。现在他行走自如,还可以在跑步机上跑步,考虑退役之后当一名警察。“如果你了解我,或者注意观察,会发现我走路还有点瘸,”他说:“但别人看到我时都会说,‘我根本想象不到(你曾经受过重伤)’。”

There is something else they would never have guessed: Sergeant Strang has grown new muscle thanks to a thin sheet of material from a pig.

还有一件事,他们恐怕更是永远也想象不到:由于取自于猪的一块薄片组织,罗恩·斯特朗已经长出了新的肌肉。

The material, called extracellular matrix, is the natural scaffolding that underlies all tissues and organs, in people as well as animals. It is produced by cells, and for years scientists thought that its main role was to hold them in their proper position.

这种材料在医学上被称为细胞外基质,在人和动物体内,它是所有组织和器官生长的天然支架复合物。它由细胞产生,多年来,科学家们认为它的主要作用是将细胞支撑在合适的位置。

But researchers now know that this scaffolding also signals the body to grow and repair those tissues and organs. Armed with that knowledge, the new body builders are using this material from pigs and other animals to engineer the growth of replacement tissue in humans.

现在研究员们认识到,这些支架复合物也向机体发出信号,使其生长、修复组织和器官。了解到这一点,研究员们利用这些取自于猪和其他动物的材料来设计人体替代组织的生长。

The technique used on Sergeant Strang, though still in development, holds particular promise for some of the thousands of veterans of the Iraq and Afghanistan wars who have been maimed by explosives and have lost so much muscle from an arm or a leg that amputation is sometimes the best alternative.

这种仍处在研发阶段的技术已经应用到了斯特朗中士的身上。成千上万的退伍军人在伊拉克和阿富汗战争中因炸弹致残,胳膊或腿失去了很多肌肉以至于不得不截肢。对于他们中的一些人来说,这种技术带来了新的希望。

Sergeant Strang’s is one of the first cases in what will eventually be an 80-patient trial to grow limb muscle. It is financed by the Defense Department’s Office of Technology Transition, but it will include civilians as well.

在80名再生肢体肌肉实验患者中,斯特朗是其中一例。研究经费由美国国防部的技术转移办公室(Defense Department’s Office of Technology Transition)提供,不过适用人群也包括了普通平民。

Dr. Peter Rubin, a plastic surgeon at the University of Pittsburgh Medical Center who is a leader of the study, said that early results with Sergeant Strang and a handful of other patients showed that the animal scaffolding was spurring muscle growth. “We are seeing evidence of remodeling of tissues,” he said.

这项研究的学科带头人是匹兹堡大学(University of Pittsburgh)医学中心的整形医生彼得·鲁宾(Peter Rubin)博士。他说斯特朗中士和其他一些患者的早期试验结果表明,支架复合体能刺激肌肉的生长。他说:“我们能找到组织重塑的证据。”

Last fall, Dr. Rubin cut out the scar tissue from Sergeant Strang’s leg and stitched a sheet resembling a thick piece of parchment paper — extracellular matrix from a pig urinary bladder, which had shown excellent results in lab studies — into the remaining healthy thigh muscle.

去年秋天,鲁宾博士切除了斯特朗中士腿上的疤痕组织,在剩下的健康大腿肌肉上缝上了一块像厚羊皮纸一样的薄片——来自于猪膀胱的细胞外基质,它在实验室研究中表现很出色。

His body immediately started breaking down the matrix, which consists largely of collagen and other proteins. But the doctors expected, and wanted, that to happen — by degrading into smaller compounds, the matrix started the signaling process, recruiting stem cells to come to the site where they could become muscle cells.

他的机体迅速开始降解基质,包括大量的胶原和其他蛋白。但医生们期待并认为会发生的是这个结果——这些基质通过降解成更小的复合物,能够启动信号传导,募集干细胞聚集到那些可以促使它们成为肌肉细胞的组织中。

“We’re trying to work with nature rather than fight nature,” said another leader of the study, Dr. Stephen Badylak, deputy director of the McGowan Institute for Regenerative Medicine at the university.

“我们的工作就是去试着顺从自然而不是去反击它,”该研究的另一位负责人、匹兹堡大学麦高恩再生医学研究所(McGowan Institute for Regenerative Medicine)的副所长斯蒂芬·贝狄拉克(Stephen Badylak)博士如是说。

Dr. Badylak is a pioneer in the use of extracellular matrix, having discovered many of its properties more than two decades ago while performing biomedical engineering research at Purdue University. As part of his work on a mechanical heart device, he was looking for a way to move blood from one part of the body to another but wanted to avoid synthetic materials, which can cause blood clots.

贝狄拉克博士是使用细胞外基质的先驱, 20多年前在普渡大学(Purdue University)进行生物医学工程研究的时候,他就发现了它的许多属性。当时他的部分工作是设计机械心脏,想要寻找一种方法将血液从身体的一部位转移到另一部分,但是要避免因合成材料导致的血液凝块。

“I thought, what looks like a tube?” he recalled. “A piece of intestine.” So using a research dog named Rocky, he replaced its main artery near its heart with a section of its small intestine. (“I’d have a tough time getting that experiment approved today,” Dr. Badylak said.)

“我当时寻思着,什么东西看起来像一根输送管道呢?一段小肠会很合适。”他回忆说。于是他用了一只名叫罗基(Rocky)的狗进行研究,用它的一段小肠代替了其心脏附近的大动脉。(“换成是今天,这种实验肯定很难通过审批,”贝狄拉克说。)

When he arrived at work the next morning, he was expecting all sorts of problems. “But Rocky is standing up in his cage, wanting breakfast and wagging his tail,” Dr. Badylak said. “I thought, well, this is pretty cool.”

手术次日,早上上班时,他的脑海里浮现出了各种状况。“可是罗基活灵活现地站在笼子里,摇着尾巴要吃早餐,”贝狄拉克说,“我当时想,好啊,这真是太酷了。”

Later experiments showed that over time the tube had lost the internal cells that are specific to intestines and gained cells specific to blood vessels. “It had morphed into a blood-vessel-like structure, which we thought was incredible,” he said. “Eventually we figured out that it was not the whole intestine but just the extracellular matrix that was responsible.”

后来的实验表明,随着时间的推移,这条输送管道已失去了特异的肠细胞,而获得了血管细胞特异性的细胞。“它已经演变成血管状结构,我们都觉得这太难以置信了,”他说,“后来我们弄清楚了,起作用的不是整段小肠,而是细胞外基质。”

Extracellular matrix from pigs, sheep and other animals has been used in the past decade as a reinforcing layer to help repair rotator cuff damage, hernias and other injuries. “Surgeons think of them as meshes that hold things together,” Dr. Badylak said. Most of them do not understand the matrix’s role in signaling and repair. “They don’t get it,” he said. “We didn’t either at first.”

细胞外基质可来源于猪、羊以及其他动物,在过去的十年里,它常常被用作增生层来治疗肩袖损伤、疝气和其他伤害。“外科医生认为他们是一种网状物,能够将物质聚合在一起,”贝狄拉克博士说。大多数医生并不明白细胞基质在通讯和修复中的作用。“他们不明白这一点,”他说,“我们一开始也没不明白。”

The scaffolding is isolated by stripping out all of the living cells from a tissue or organ, leaving an intricate three-dimensional web of proteins and other compounds. Removing the cells eliminates the possibility that the material, of animal origin, will be rejected outright by the body when it is implanted. But the matrix does provoke a less intense immune response, Dr. Badylak said, which is necessary for it to work. “You actually need the immune system to recognize the material.”

这种脚手架材料通过剥离所有组织或器官的活细胞,留下一个复杂的立体网状,里面是蛋白质和其它化合物。去除细胞,这就消除了来源于动物的材料植入人体内时被排异的可能性。而基质所诱发的免疫反应的确弱的多。狄拉克博士说,这种弱免疫反应是必要的,这样才能使其发挥作用。“你需要让免疫系统识别这个材料。”

“The body can say, ‘This is not me,’ but the signals that are there are actually telling me that I need to rebuild that tissue,” he added.

“如果身体会说话,它一定会说‘这玩意儿不是我身上的东西,’但实际上信号的出现告诉我,我要重塑组织。”他补充道。

The matrix has to be in contact with healthy tissue, which is why scar tissue must be removed first. “If it’s put in the middle of a scar, it doesn’t remodel because it’s not exposed to the bloodstream and sources of cells,” Dr. Badylak said.

这种基质需要去接触那些健康的组织,这也是科学家必须首先除去疤痕组织的原因。“如果我们把基质放到疤痕之中,基质将不再重塑,因为它没有接触到血液和细胞的来源。”狄拉克博士说。

Stitching it directly to the muscle also ensures that it will be stretched when the muscle is activated, beginning the day after surgery, when patients start an intensive program of physical therapy. Putting a mechanical load on the matrix tells the body, in effect, that this should become muscle and not some other kind of tissue.

直接缝合肌肉也可以确保在术后第二天,患者开始接受强化物理治疗时,激活的肌肉能够被拉伸开来。将机械负荷加到基质上能有效地将这个信息反馈给身体:它将成为新的肌肉组织,而不是其他类型的组织。

Sergeant Strang was skeptical when he first signed up for the trial and cleared all the physical hurdles to qualify for it — among other things, patients must have some muscle remaining and enough undamaged nerves so the muscle can work. But at that point he was willing to try anything to be able to walk normally again.

当斯特朗中士起初同意参加这个试验,并克服了各种身体障碍,达到试验要求时,他也曾产生过很多疑虑,其中一点是他怀疑参加这个试验,患者还必须有一定的肌肉和充足的未损坏的神经,以便肌肉可以再生。但在那时,他愿意尝试任何事情,只要能重新正常行走就行。

Ten soldiers, American and Afghan, were wounded on the road in Helmand Province that Easter Sunday, Sergeant Strang the most severely. He was given 42 units of blood, airlifted to Germany and then treated for a month at Walter Reed Army Medical Center in Bethesda, Md.

复活节那天,十个士兵——包括美国人和阿富汗人,在赫尔曼德省的道路上受伤,斯特朗伤势最重。医生给他输了42个单位(1单位为200毫升——译注)的血液并空运到德国,然后在马里兰州贝塞斯达的沃尔特·里德陆军医疗中心(Walter Reed Army Medical Center)治疗了一个月时间。

Sergeant Strang returned to his home outside Pittsburgh, where he underwent outpatient physical therapy for months. When he walked he favored his right leg, which caused pain in his knees, back, hip and neck. “Everything was torqued to the side,” he said.

斯特朗回到了位于匹兹堡郊外的老家,在那里他接受数月的门诊物理治疗。走路时,他只能把重心放在右腿上,这让他双腿的膝盖、后背、臀部和颈部疼痛。“身体每个部位都被扭到一边,”他说。

When the doctors told him what they planned to do, “I kind of didn’t believe it at first,” Sergeant Strang said. “It strikes you as science fiction stuff when they explain it to you.”

当医生向他介绍他们的方案时,“一开始我有点无法相信这种事情,”斯特朗中士说,“当他们跟我解释的时候,我被震到了,听起来就像科幻小说里的东西。”

Dr. Badylak said it was important not to set unrealistic expectations.

贝狄拉克博士说,最重要的是它不是那种不切实际的期望。

“We tell them, this isn’t magic. It’s not a miracle,” he said. “We’re not going to restore your 100 percent normal anatomy. But we think we’re going to be able to make a difference for you. You’ll be able to do things you can’t do now.”

“我们告诉他们,这不是魔法,也不是奇迹,”他说,“我们可能做不到百分之百恢复你的正常解剖结构,但是我们认为我们将会给你带来巨大的变化,你将能够做到那些你现在无法完成的事情。”

There is still a big divot in Sergeant Strang’s leg, graphically illustrating how just a little new muscle tissue can make a difference.

现在斯特朗的大腿上仍然有一块很大的凹陷,它形象地说明了一小块新的肌肉组织能带来怎样的不凡成果。

“It was amazing,” he said. “Right off the bat I could do a full stride, I could bend my knee, kick it out a little bit, just enough to get that initial spring where gravity would take it the rest of the way.” Two weeks later he was out in the woods hunting with friends.

“太神奇了,”他说,“很快我就可以跨一大步,我可以弯曲我的膝盖,踢出一小步,然后因为重力作用它又可以返回初始状态。”手术两个星期后,他与朋友外出,在森林狩猎。

Some of the initial improvement may be from the mechanical connection between the matrix and the existing muscle, the doctors said. But as the matrix has degraded, Sergeant Strang has continued to improve, although there are signs that his progress is slowing down.

医生们说,初步的进展可能是从基质与现存组织的机械连接开始,但是当基质分解退化后,尽管有迹象表明变化的步调放缓,斯特朗的身体仍然在不断改善。

The improvement had a psychological effect, too, Sergeant Strang said. Before, if he went to a busy restaurant or other crowded place, he would spend time planning where to sit, because he knew he would not be able to move quickly in the event of danger. “It was always in the back of my mind,” he said.

斯特朗中士说,这种改善也会产生心理效应。在此之前,如果他要去一家生意很好的餐厅或者其他拥挤的地方,他可能会花费很多的时间去决定坐在哪里,因为他知道一旦发生险情,他无法迅速撤离。“这种顾虑老是徘徊在我的脑海中,”他说。

But now, he said, “I don’t have to sit by the door.”

“但是现在,”他说,“我没有必要坐在门口了。”
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