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Stem-cell therapies —— Prometheus unbound
幹細胞治療:普羅米修斯自由瞭
Researchers have yet to realise the old dream of regenerating organs. But they are getting closer
亙古以來,器官再生便是人類的夙願。如今研究人員雖然還未真正實現,但成功的腳步已經越來越近
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PROMETHEUS, a Titan bound to a rock by Zeus, endured the daily torture of an eagle feasting on his liver, only to have the organ regrow each night.
在希臘神話之中,提坦普羅米修斯被宙斯束縛在一塊巨石之上,白天忍受著老鷹啄食他的肝臟,夜晚他的肝臟卻又總會再次生長。
Compared with this spectacle, a video on the website of Nature seems decidedly dull.
與生動的故事情節相比,《自然》網站上的一段視頻就顯得如此枯燥。
It shows a collection of pink dots consolidating into a darker central glob.
這段視頻向世人展示瞭無數粉紅色的小點向中心聚攏,成為一個顏色更深的團狀物的過程。
But something titanic is indeed happening.
但這正是普羅米修斯自由的曙光。
The pink dots are stem cells, and the video shows the development of a liver bud, something which can go on to look and act like a liver.
那些粉紅色的小點就是幹細胞,而視頻顯示的正是肝芽生長的過程,並且這個肝芽可以進一步發育為,無論是外表還是功能都與肝臟類似的組織。
Takanori Takebe and Hideki Taniguchi of Yokohama City University, in Japan, who made the video, have created working human-liver tissue.
日本橫濱市立大學的武部孝則和谷口英機拍攝瞭這段視頻,這次他們培養出瞭具有功能性的人類肝臟組織。
Researchers have long dreamed that stem cells might be used to repair or replace damaged tissue, an aspiration known as regenerative medicine.
研究人員長期以來都設想幹細胞能夠用來修復或替換受損組織,該研究領域則被冠名為再生醫學。
Embryonic stem cells, in particular, are pluripotent, meaning they are able to become any other type of cell.
多能的胚胎幹細胞被再生醫學傢們寄予厚望,所謂多能就意味著這些幹細胞可以分化出多種其他類型的細胞。
And it is now possible to induce pluripotency in cells that have not come from embryos, thus circumventing the ethical minefield previously associated with obtaining them.
現在的技術已經可以在非胚胎細胞中誘導細胞的多能性,這樣就可以繞過之前直接使用胚胎細胞時所引發的倫理爭議。
Last year Shinya Yamanaka of Kyoto University won a Nobel prize for the invention of induced pluripotency.
日本京都大學的山中伸彌由於成功誘導細胞的多能性而於去年榮獲諾貝爾獎。
He had shown how four signal proteins can reprogram adult cells into a pluripotent state.
他公開發表瞭借助四種信號蛋白,重組成人細胞並使其具有多能性的實驗過程。
Beside dealing with the ethical problems of embryonic cells, Dr Yamanaka's induced pluripotent stem cells allow — at least in theory — a treatment to be created from a patient's own body.
除瞭成功躲開瞭胚胎細胞的倫理問題,山中博士發明的誘導多能幹細胞,使得再生醫學可以從患者體內提取細胞進行再生治療。
This would have his own genetic make up and would thus not attract the attention of his immune system.
這樣就可以取得患者自身的基因組合,避免瞭患者免疫系統的排異反應。
Realising such treatments has been fiendishly difficult.
要真正實現這種幹細胞治療仍然困難重重,
But Dr Takebe's paper in Nature is one of several signs that the Promethean dream is slowly coming to life.
但是武部博士發表於《自然》的論文則是人類又一次向解放普羅米修斯邁出瞭堅實的一步。
Budding hope
星星之火
Clinical trials of pluripotent cells are already happening, though they hark back to the days when only cells derived from embryos were available.
多能細胞的臨床試驗其實早已開始進行,隻是這種多能細胞還是由胚胎幹細胞所培養。
An American firm called Advanced Cell Technology is using them to treat macular degeneration, a cause of blindness.
美國先進細胞技術公司正運用多能細胞治療可能致盲的黃斑變性。
Last year it reported promising results in two patients and Gary Rabin, the firm's boss, says tests continue.
去年該公司報告瞭兩例有望好轉的臨床病患,公司老總加裡 · 拉賓也表示,試驗仍會繼續。
Even if this specific approach works, though, it is likely to be overtaken by iPS technology.
不過,即使這一臨床試驗終獲成功,也有可能會被 iPS 技術所取代。
The Japanese, not surprisingly, are in the lead.
日本在 iPS 技術方面無疑領先於世界其他各國。
Soon, the country's health ministry is expected to approve the first clinical trial of iPS cells, also for macular degeneration.
該國衛生部應該不久便會批準 iPS 細胞的第一例臨床試驗,同樣也是治療黃斑變性。
But ACT is not far behind.
然而 ACT 也並未脫離戰隊,
It hopes to begin a trial of platelets made from iPS cells.
該公司希望開始一項 iPS 細胞培養血小板的試驗。
And other firms want to treat everything from Parkinson's disease to glaucoma to multiple sclerosis.
還有些公司則希望透過 iPS 技術治療其他疾病,包括帕金森病、青光眼、多發性硬化等。
Academia is pushing ahead as well.
學術界則正在進一步地研究 iPS 技術。
Inspired by Dr Yamanaka's work, people are looking for other shortcuts to pluripotency.
受到山中教授研究成果的啟發,人們紛紛開始探究誘導細胞多能性更為便捷的其他途徑。
Marius Wernig of Stanford University, for instance, has worked out how to use three proteins to turn connective-tissue cells into neurons.
斯坦福大學的馬呂斯 · 維米格就發現瞭使用三種蛋白質,將結締組織細胞轉化為神經細胞的方法。
Deepak Srivastava of the University of California, San Francisco, meanwhile, has shown how to convert connective tissue into heart cells.
加州大學舊金山分校的迪帕克 · 司裡瓦斯德瓦則發表瞭將結締組織轉化為心肌細胞的過程。
Other research is going beyond simple cell cultures.
還有一些研究就沒有局限於簡單的細胞培養領域。左使良樹任職於神戶的理化研究所發育生物學中心。
Yoshiki Sasai of the RIKEN Centre for Developmental Biology, in Kobe, showed how mouse embryonic stem cells, if mixed with a few appropriate growth factors, quickly form a three-dimensional cluster made of the precursor cells to neurons.
他發表論文闡述瞭老鼠胚胎幹細胞在給予一些適當的生長因子後,快速形成一個三維立體簇集物的過程。
This cluster then turns into something resembling the back of an eye.
而這種簇集物由多種細胞構成,並進而發育成一種類似於眼底結構的組織。
Last year Dr Sasai repeated the trick with human cells.
去年左使博士使用人類細胞再次重復瞭這一實驗過程。
The dream is to make a complex organ from scratch.
人們的夢想就是從無到有地創造出一個復雜的器官。
With this in mind researchers at Wake Forest University in North Carolina have used a three-dimensional printer to produce an artificial kidney using immature kidney cells.
為瞭實現這個夢想,北卡羅來納州維克森林大學的研究員們使用三維打印技術,用不成熟的腎臟細胞做出瞭一個人造腎臟。
But if such organs are to work in people, they will need blood vessels to deliver oxygen and nutrients.
不過要讓這樣的腎臟在人體內正常工作,其中還是缺少瞭用於輸送氧氣和營養物質的血管。
The way to do that might, paradoxically, be for scientists to do less. Instead of making the whole organ in a laboratory, they might create a less-developed form, as Dr Sasai did with his proto-retina, and then leave the rest of the work to the body.
如果真要實現這個夢想,科學傢可能用不著在腎臟中再造血管—這聽起來可能有些自相矛盾—他們其實不必在實驗室中造出完整的人體器官。科學傢可以先造出還沒發育完全的器官試樣,然後在活體體內完成剩下的研究工作。
This is what Dr Takebe has done with his liver buds.
武部博士的肝芽生長研究正是遵照這樣的器官再造思路而完成的。
He coaxed some iPS cells into becoming liver endodermal cells.
他小心地將一些 iPS 細胞導入合適的肝臟內胚層細胞。
He then cultured them with two other cell types: endothelial cells, which make up the inner linings of blood vessels, that were derived from umbilical cord; and mesenchymal stem cells, derived from bone marrow, which can differentiate into several kinds of cells, though not as many as pluripotent cells.
然後將這些肝臟內胚層細胞與其他兩種細胞一起培養。一種是取自臍帶的內皮細胞,這種細胞構成瞭血管內層 ; 另一種細胞是取自骨髓的間充質幹細胞,這種細胞可以分化成多種細胞類型。
Cultures without mesenchymal stem cells failed to form a cluster.
實驗證明,如果培養過程中缺少間充質幹細胞,就不會形成簇集物 ;
Those without endothelial cells failed to create a network of blood vessels.
而如果沒有內皮細胞,就無法形成血管網絡。
But together, the three types of cell, with little additional prodding, formed a bud within two days.
隻有將肝臟內胚層細胞與這兩者結合,並配合少量的其他刺激,才最終能在兩天內形成肝芽。
At six days this bud was expressing genes known to be early markers of the liver.
到瞭第六天,肝芽開始表達一些在肝臟早期形成階段具有標志性的基因。
And when Dr Takebe implanted such buds into the brains of mice whose immune systems had been disabled to prevent rejection, he observed that they connected with the mouse's blood system within two days.
隨後,武部博士將這些肝芽結構植入一些喪失免疫能力的老鼠的腦中,這樣老鼠就不會對肝芽組織形成排斥反應。武部博士發現,兩天內肝芽結構就與這些老鼠腦中的血液循環系統相互融合瞭。
After two months the buds not only looked like liver, they acted like it.
兩個月後,肝芽結構除瞭看上去像肝臟外,也具有瞭肝臟的生理功能—他們產生出瞭肝臟獨有的蛋白質。
They produced liver-specific proteins. And if Dr Takebe transplanted them to their host's abdominal cavity, having first caused the animal's real liver to fail, they often kept the mouse alive when an animal without the transplant would have died.
然後武部博士又將這些肝芽結構移植到瞭相應老鼠的腹腔中,起初肝芽結構會破壞老鼠體內自身的肝臟,但是接著很多老鼠並沒有死亡。
Translating this work into a way of growing new livers for people whose old ones have stopped working will take time.
誠然,要將這個過程在人類身上臨床試驗仍需時日。
But it is a big step forward.
但在老鼠體內的實驗已是繼往開來的重要一步。
After years of promise, regenerative medicine may be coming close to delivering.
在人們年復一年的期盼中,再生醫療終會有實現夢想的那一天。
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