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更新时间:2014-4-24 14:45:51 来源:华尔街日报中文网 作者:佚名

Scientists Progress In Quest To Grow Muscle Tissue

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.

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.

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.

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.

'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.

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.

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.

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.

'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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

杜克大学(Duke University)的研究人员和其他科学家在利用实验室培育肌肉方面取得了很大的进展。这些肌肉不仅自我修复,还展现出与正常肌肉相近的力量。




这个领域内的先驱、布朗大学(Brown University)病理学与检验医学荣誉教授赫尔曼·范登伯格(Herman Vandenburgh)说:“障碍在于有没有一个创伤去努力获得能够比瘢痕组织更快形成的新肌肉组织。”




杜克大学生物医学工程学教授内纳德·布尔萨奇(Nenad Bursac)说:“没有结构,就没有功能。”

布尔萨奇和包括第一作者、研究生马克·尤哈斯(Mark Juhas)在内的团队第一次在动物身上证明,他们可以利用干细胞生成自我修复并逐渐变强的肌肉组织。

3月下旬,团队将实验结果发表在《美国国家科学院院刊》(Proceedings of the National Academy of Sciences)上。






布朗大学的范登伯格博士等一些科学家则利用不同的干细胞处理方法取得了明显的进展。他们侧重于在植入人类干细胞的时候利用适合的生物化学调和物来刺激生长。范登伯格博士跟哈佛大学(Harvard University)戴维·穆尼(David Mooney)团队一起合作。





布尔萨奇说,因为肌肉组织非常紧密,很难让足量的氧和血液流到组织内部的肌肉上去。他和其他研究人员(比如华盛顿大学 路易斯分校(Washington University in St. Louis)的研究人员)正在想办法在肌肉组织中开辟出能够输送肌肉所需营养物质的通道。