人工培育肌肉組織研究獲重大進展

Duke University researchers and other scientists are making strides in growing muscle in the lab that not only repairs itself but exhibits strength similar to that of normal muscle.

Duke University這幅放大影像顯示了植入老鼠體內兩週之後的實驗室肌肉纖維。這些纖維通過染色標明瞭不同的蛋白。杜克大學(Duke University)的研究人員和其他科學家在利用實驗室培育肌肉方面取得了很大的進展。這些肌肉不僅自我修復，還展現出與正常肌肉相近的力量。

Using lab-grown muscle could one day help people with certain muscle injuries, including accident victims with big gashes that lead to significant scar tissue. Engineering muscle that works like natural tissue could also accelerate the testing of new drugs: Scientists could use this tissue in place of animals.

有朝一日，利用從實驗室培育的肌肉可能能夠幫到有某些肌肉創傷的人，比如因爲大傷口而長出明顯瘢痕組織的事故受害者。製造出像天然肌肉一樣發揮作用的肌肉，還有可能加快新藥的測試，因爲科學家可以用這類組織來替代動物。

Scientists have succeeded in developing ears, windpipes and livers, among other body parts, and even implanted some into humans. Muscle is among the more challenging because the fibers need to have the right structure and fit densely together. It must also be able to contract and exert force like natural muscle. And it needs good blood supply to cells, which can be difficult because muscle is very dense.

科學家已經成功地培育了耳朵、氣管、肝臟等人體器官，甚至把一些器官移植到人類身上。培育肌肉的挑戰更大，因爲肌肉纖維必須擁有合適的結構，從而能夠緊密地結合在一起。它還要能夠像天然肌肉一樣收縮、發力，其細胞需要擁有充足的血液供應，而由於肌肉非常緊密，這一點有時候很難實現。

Skeletal muscle, the most abundant tissue in the body, typically is very good at repairing itself because it contains many adult stem cells that can create new muscle fibers. With diseases like muscular dystrophy or injuries that cause scar tissue, muscle stops being able to regenerate, which can lead to difficulty moving or even paralysis. Scar tissue, made of collagen, doesn't generate force and thus weakens the muscle. During normal aging, muscles also become weaker and gradually cease being able to repair themselves.

Nenad Bursac杜克大學生物化學工程學教授內納德•布爾薩奇。人體最豐富的組織骨骼肌往往非常善於自我修復，因爲它含有很多成年幹細胞，可以生成新的肌肉纖維。如果有肌肉萎縮等疾病或形成瘢痕組織的傷口，肌肉就不再能夠再生，有可能導致行動困難，甚至是癱瘓。由膠原質組成的瘢痕組織不產生力量，因此對肌肉起到削弱作用。在正常衰老過程中，肌肉也會變得越來越弱，並逐漸失去自我修復的能力。

'The hurdle is if there is an injury to try to get new muscle tissue that can form quicker' than scar tissue, says Herman Vandenburgh, a pioneer in the field and a professor emeritus of pathology and laboratory medicine at Brown University.

這個領域內的先驅、布朗大學(Brown University)病理學與檢驗醫學榮譽教授赫爾曼·範登伯格(Herman Vandenburgh)說：“障礙在於有沒有一個創傷去努力獲得能夠比瘢痕組織更快形成的新肌肉組織。”

For about two decades, scientists have been trying to grow muscle in the lab that exerts force and repairs itself, in hopes of one day helping to restore functioning in patients. Understanding the process of muscle regeneration may lead to better understanding of the muscle-wasting process that occurs with aging or disease.

大約20年以來，科學家一直試圖在實驗室裏培育能夠使力並自愈的肌肉，希望有朝一日幫助恢復病人的機能。明白了肌肉再生的過程，或許就能更好地理解伴隨衰老或疾病而發生的肌肉萎縮。

Researchers approach muscle regeneration in different ways, with some growing tissue in the lab that is then used to repair injuries. Others focus on finding genes or a drug that could reverse muscle wasting across the body.

研究人員用不同的方法來實現肌肉再生。一些人是在實驗室培育肌肉組織，然後用這些組織來修復傷口，另一些人則是側重於尋找有望逆轉全身肌肉萎縮過程的基因或藥物。

To develop functional muscle, both the structure of the muscle tissue and how it's connected to the blood supply and nerves in the spinal cord are critical. Muscle tissue is dense and made of large muscle cells aligned in the same direction. Without the correct alignment and density, muscle cells can't generate the force they need to power a limb, for instance.

爲了培育擁有機能的肌肉，肌肉組織的結構以及它與血液供應和脊髓神經的連接方式都是至關重要的。肌肉組織很緊密，由同向排列的大型肌肉細胞組成。如果排列方式和密度不合適，肌肉細胞就無法產生移動肢體等所需要的力量。

'If you're off with [the structure], then you'll be off with function,' says Nenad Bursac, a professor of biomedical engineering at Duke University.

杜克大學生物醫學工程學教授內納德·布爾薩奇(Nenad Bursac)說：“沒有結構，就沒有功能。”

Dr. Bursac and his team, including first author Mark Juhas, a graduate student, demonstrated for the first time in animals that they could use stem cells to create muscle tissue that repaired itself and grew stronger.

布爾薩奇和包括第一作者、研究生馬克·尤哈斯(Mark Juhas)在內的團隊第一次在動物身上證明，他們可以利用幹細胞生成自我修復並逐漸變強的肌肉組織。

The team published the results in late March in the Proceedings of the National Academy of Sciences.

3月下旬，團隊將實驗結果發表在《美國國家科學院院刊》(Proceedings of the National Academy of Sciences)上。

They also used a new technique for watching the tissue grow by creating a 'window' in the backs of mice that allowed them to see into the animals without harming them and watch the muscle cells regenerate before their eyes.

他們還利用一種新技術來觀察組織的生長，具體辦法是在老鼠背部打開一個“窗口”，從而能夠在不傷害動物的情況下察看其內部，看着肌肉細胞在眼前再生。

First, they took muscle tissue from rats and isolated the stem cells, which are the cells that grow into muscle tissue throughout life. Then, after growing more stem cells, they were mixed with a substance containing fibrinogen naturally found in blood clots to help the cells bind together. The combination was placed in a cylindrical mold so that the cells formed long, cylindrical tissue, mimicking the shape of natural muscle.

首先，他們從老鼠身上取下肌肉組織，將幹細胞（在生命週期中長成肌肉組織的細胞）分離出來。在培育出更多幹細胞之後，就把這些細胞跟一種包含纖維蛋白原的物質混合在一起。（纖維蛋白原天然地存在於血液凝塊中，有助於細胞組合在一起）。然後將混合物放進一個圓柱形模具裏，讓細胞形成長長的圓柱形組織，模仿天然肌肉的形狀。

The scientists tested the tissue in two ways: In a dish, researchers stressed the tissue by applying a toxin to it that destroyed a number of muscle fibers, and then watched to see if the fibers regrew.

科學家用兩種方法測試培育出來的組織。研究人員在一個培養皿裏給肌肉組織施放一種毒質，破壞掉一定數量的肌肉纖維，然後看纖維會不會重新生長。

The fibers did regenerate. Within 10 days after injury, the muscle regained 80% to 90% of its strength. In a separate experiment, scientists implanted the tissue into a mouse that had a 9-millimeter-wide portal implanted in its back. Within two weeks that tissue increased its strength threefold, into the range of normal muscle strength, Dr. Bursac says.

纖維真的再生了。在受傷之後10天內，肌肉恢復了80%到90%的力量。在另一項實驗中，科學家將組織植入一隻之前在背上植入了一個9毫米寬入口的老鼠。布爾薩奇說，兩個星期之內，組織力量增加到原來的三倍，達到了正常肌肉力量的範圍。

The group also replicated the work using human muscle stem cells in a dish, though that work hasn't yet been published, according to Dr. Bursac. The researchers are now working on optimizing the growth of human muscle tissue, including finding a way to get blood flow to the tissue, the best source of cells and the best growing medium for the cells.

據布爾薩奇說，團隊還利用人類肌肉乾細胞在一個培養皿中重複了上述實驗，不過實驗結果還沒有發表。研究人員目前正在着手完善人類肌肉組織的培養，比如想辦法讓血液流入組織，找到最好的細胞源，以及爲細胞尋找最好的生長介質等。

Other scientists, such as Brown's Dr. Vandenburgh, working with David Mooney's team at Harvard University, have made significant strides using a different stem-cell approach, focusing on implanting human stem cells using the right concoction of biological chemicals to stimulate growth.

布朗大學的範登伯格博士等一些科學家則利用不同的幹細胞處理方法取得了明顯的進展。他們側重於在植入人類幹細胞的時候利用適合的生物化學調和物來刺激生長。範登伯格博士跟哈佛大學(Harvard University)戴維·穆尼(David Mooney)團隊一起合作。

Taking biopsies from adult volunteers, including the muscle cells of individuals with congestive heart failure and the frail elderly, and implanting those stem cells into mice, they have been able to demonstrate that they can grow muscle tissue that generates about 90% to 95% of the force of a normally functioning muscle fiber.

他們在成年志願者身上採集活組織標本（包括充血性心力衰竭患者和體弱老年人身上的肌肉細胞），然後把這些幹細胞植入老鼠體內，得以證明他們培育出的肌肉組織大約可以達到機能正常肌肉纖維90%到95%的力量。

Dr. Vandenburgh estimates that the technique could be ready for human clinical trial testing within four to five years. The approach will be best for someone with a specific weakened muscle rather than someone with a disease that causes general muscle wasting, he says.

範登伯格估計，這項技術有望在四五年之內達到做人類臨牀試驗的條件。他說，這一方法將最適合某些肌肉受損的人，而不是身患某種疾病、導致肌肉總體萎縮的人。

Early trials could target drooping eyelids, for example, by injecting the stem cells into the muscle around the eye. The hope would be for the healthy stem cells to migrate to the wounded tissue and regenerate it.

早期試驗可能會以下垂的眼瞼爲目標，比如說向眼部周圍的肌肉注入幹細胞，希望健康幹細胞能夠進入受損組織，使之重新生長。

Another challenge to using regenerated muscle for therapeutic purposes is the size of the tissue that can be regenerated, experts say. For instance, the mouse calf muscle generated by the team currently is about 20 millimeters long and 4 to 5 millimeters wide, a fraction of the human calf muscle.

專家說，使用再生肌肉用於治療目的另一重挑戰在於能夠再生的組織的大小。比如團隊目前培育的老鼠腓腸肌約爲20毫米長，4到5毫米寬，只佔人類腓腸肌的很小一部分。

Because muscle tissue is very dense, it's difficult to get enough oxygen and blood flow to the muscle on the inside of the tissue, Dr. Bursac says. He and other researchers, such as those at Washington University in St. Louis, are trying to create channels in muscle tissue that can deliver the nutrients the muscle needs.

布爾薩奇說，因爲肌肉組織非常緊密，很難讓足量的氧和血液流到組織內部的肌肉上去。他和其他研究人員（比如華盛頓大學 路易斯分校(Washington University in St. Louis)的研究人員）正在想辦法在肌肉組織中開闢出能夠輸送肌肉所需營養物質的通道。

If they solve this issue, doctors would be able to grow denser and stronger lab-generated muscle tissue. Resolving the issue of how to vascularize muscle tissue will open doors for the treatment potential of regenerated muscle tissue, Dr. Bursac says.

如果他們解決了這個問題，醫生將能夠培育出更加緊密、更有力量的實驗室肌肉組織。布爾薩奇說，解決了怎樣給肌肉組織建造血管的問題，就會爲再生肌肉組織的治療潛能開閘。

Shirley S. Wang

Shirley S. Wang