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在動物組織上生長出的人類肌肉

Human Muscle, Regrown on Animal Scaffolding
在動物組織上生長出的人類肌肉

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.

匹茲堡——阿富汗路邊的炸彈炸掉了羅恩·斯特朗(Ron Strang)中士左腿的部分肌肉,在那之后的幾個月,他懷疑這輩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.

爆炸和連續數次的手術,在28歲的海軍陸戰隊員斯特朗中士的大腿的四頭肌上留下了一道巨大的傷口。由于失去大量的肌肉組織,他的腿只能向后移動,不能向前踢。他可以行走,但動作很笨拙。

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

“我那時練得特別擅長臥倒,”他談到了自己歷經的艱辛。羅恩·斯特朗中士身材高大健碩,他不得不放棄跑步。
 

羅恩·斯特朗與女友莫妮卡·米奇娜(Monica Michna)一起鍛煉。他在阿富汗服役時,左腿四頭肌部分被炸彈炸飛。

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.’ ”

但是那是兩年前?,F在他行走自如,還可以在跑步機上跑步,考慮退役之后當一名警察。“如果你了解我,或者注意觀察,會發現我走路還有點瘸,”他說:“但別人看到我時都會說,‘我根本想象不到(你曾經受過重傷)’。”

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.

還有一件事,他們恐怕更是永遠也想象不到:由于取自于豬的一塊薄片組織,羅恩·斯特朗已經長出了新的肌肉。

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.

這種材料在醫學上被稱為細胞外基質,在人和動物體內,它是所有組織和器官生長的天然支架復合物。它由細胞產生,多年來,科學家們認為它的主要作用是將細胞支撐在合適的位置。

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.

現在研究員們認識到,這些支架復合物也向機體發出信號,使其生長、修復組織和器官。了解到這一點,研究員們利用這些取自于豬和其他動物的材料來設計人體替代組織的生長。

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.

這種仍處在研發階段的技術已經應用到了斯特朗中士的身上。成千上萬的退伍軍人在伊拉克和阿富汗戰爭中因炸彈致殘,胳膊或腿失去了很多肌肉以至于不得不截肢。對于他們中的一些人來說,這種技術帶來了新的希望。

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名再生肢體肌肉實驗患者中,斯特朗是其中一例。研究經費由美國國防部的技術轉移辦公室(Defense Department’s Office of Technology Transition)提供,不過適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.

這項研究的學科帶頭人是匹茲堡大學(University of Pittsburgh)醫學中心的整形醫生彼得·魯賓(Peter Rubin)博士。他說斯特朗中士和其他一些患者的早期試驗結果表明,支架復合體能刺激肌肉的生長。他說:“我們能找到組織重塑的證據。”

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,魯賓博士切除了斯特朗中士腿上的疤痕組織,在剩下的健康大腿肌肉上縫上了一塊像厚羊皮紙一樣的薄片——來自于豬膀胱的細胞外基質,它在實驗室研究中表現很出色。

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.

他的機體迅速開始降解基質,包括大量的膠原和其他蛋白。但醫生們期待并認為會發生的是這個結果——這些基質通過降解成更小的復合物,能夠啟動信號傳導,募集干細胞聚集到那些可以促使它們成為肌肉細胞的組織中。

“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.

“我們的工作就是去試著順從自然而不是去反擊它,”該研究的另一位負責人、匹茲堡大學麥高恩再生醫學研究所(McGowan Institute for Regenerative Medicine)的副所長斯蒂芬·貝狄拉克(Stephen Badylak)博士如是說。

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.

貝狄拉克博士是使用細胞外基質的先驅, 20多年前在普渡大學(Purdue University)進行生物醫學工程研究的時候,他就發現了它的許多屬性。當時他的部分工作是設計機械心臟,想要尋找一種方法將血液從身體的一部位轉移到另一部分,但是要避免因合成材料導致的血液凝塊。

“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.)

“我當時尋思著,什么東西看起來像一根輸送管道呢?一段小腸會很合適。”他回憶說。于是他用了一只名叫羅基(Rocky)的狗進行研究,用它的一段小腸代替了其心臟附近的大動脈。(“換成是今天,這種實驗肯定很難通過審批,”貝狄拉克說。)

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.”

手術次日,早上上班時,他的腦海里浮現出了各種狀況。“可是羅基活靈活現地站在籠子里,搖著尾巴要吃早餐,”貝狄拉克說,“我當時想,好啊,這真是太酷了。”

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.”

后來的實驗表明,隨著時間的推移,這條輸送管道已失去了特異的腸細胞,而獲得了血管細胞特異性的細胞。“它已經演變成血管狀結構,我們都覺得這太難以置信了,”他說,“后來我們弄清楚了,起作用的不是整段小腸,而是細胞外基質。”

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.”

細胞外基質可來源于豬、羊以及其他動物,在過去的十年里,它常常被用作增生層來治療肩袖損傷、疝氣和其他傷害。“外科醫生認為他們是一種網狀物,能夠將物質聚合在一起,”貝狄拉克博士說。大多數醫生并不明白細胞基質在通訊和修復中的作用。“他們不明白這一點,”他說,“我們一開始也沒不明白。”

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.”

這種腳手架材料通過剝離所有組織或器官的活細胞,留下一個復雜的立體網狀,里面是蛋白質和其它化合物。去除細胞,這就消除了來源于動物的材料植入人體內時被排異的可能性。而基質所誘發的免疫反應的確弱的多。狄拉克博士說,這種弱免疫反應是必要的,這樣才能使其發揮作用。“你需要讓免疫系統識別這個材料。”

“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.

“如果身體會說話,它一定會說‘這玩意兒不是我身上的東西,’但實際上信號的出現告訴我,我要重塑組織。”他補充道。

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.

這種基質需要去接觸那些健康的組織,這也是科學家必須首先除去疤痕組織的原因。“如果我們把基質放到疤痕之中,基質將不再重塑,因為它沒有接觸到血液和細胞的來源。”狄拉克博士說。

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.

直接縫合肌肉也可以確保在術后第二天,患者開始接受強化物理治療時,激活的肌肉能夠被拉伸開來。將機械負荷加到基質上能有效地將這個信息反饋給身體:它將成為新的肌肉組織,而不是其他類型的組織。

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.

當斯特朗中士起初同意參加這個試驗,并克服了各種身體障礙,達到試驗要求時,他也曾產生過很多疑慮,其中一點是他懷疑參加這個試驗,患者還必須有一定的肌肉和充足的未損壞的神經,以便肌肉可以再生。但在那時,他愿意嘗試任何事情,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.

復活節那天,十個士兵——包括美國人和阿富汗人,在赫爾曼德省的道路上受傷,斯特朗傷勢最重。醫生給他輸了42個單位(1單位為200毫升——譯注)的血液并空運到德國,然后在馬里蘭州貝塞斯達的沃爾特·里德陸軍醫療中心(Walter Reed Army Medical Center)治療了一個月時間。

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茲堡郊外的老家,在那里他接受數月的門診物理治療。走路時,他只能把重心放在右腿上,這讓他雙腿的膝蓋、后背、臀部和頸部疼痛。“身體每個部位都被扭到一邊,”他說。

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.”

當醫生向他介紹他們的方案時,“一開始我有點無法相信這種事情,”斯特朗中士說,“當他們跟我解釋的時候,我被震到了,聽起來就像科幻小說里的東西。”

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

貝狄拉克博士說,最重要的是它不是那種不切實際的期望。

“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.”

“我們告訴他們,這不是魔法,也不是奇跡,”他說,“我們可能做不到百分之百恢復你的正常解剖結構,但是我們認為我們將會給你帶來巨大的變化,你將能夠做到那些你現在無法完成的事情。”

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

現在斯特朗的大腿上仍然有一塊很大的凹陷,它形象地說明了一小塊新的肌肉組織能帶來怎樣的不凡成果。

“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,”他說,“很快我就可以跨一大步,我可以彎曲我的膝蓋,踢出一小步,然后因為重力作用它又可以返回初始狀態。”手術兩個星期后,他與朋友外出,在森林狩獵。

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.

醫生們說,初步的進展可能是從基質與現存組織的機械連接開始,但是當基質分解退化后,盡管有跡象表明變化的步調放緩,斯特朗的身體仍然在不斷改善。

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.

斯特朗中士說,這種改善也會產生心理效應。在此之前,如果他要去一家生意很好的餐廳或者其他擁擠的地方,他可能會花費很多的時間去決定坐在哪里,因為他知道一旦發生險情,他無法迅速撤離。“這種顧慮老是徘徊在我的腦海中,”他說。

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

“但是現在,”他說,“我沒有必要坐在門口了。”
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