【英语科技】鼠肺成功实现实验室再造

Scientists have made rat lungs in the laboratory, a small but tantalizing step in the quest to create body parts for transplantation or to treat disease.

A team led by researchers from Yale University took apart rats' lungs and rebuilt them with new cells in a glass jar. When transplanted into live rats for a few hours, the new organs successfully exchanged oxygen and carbon dioxide, just as natural lungs do. The findings are published in the online version of the journal Science.

The study, funded by Yale and the National Institutes of Health, builds on a handful of groundbreaking experiments of recent years. A breakthrough using the same technique occurred in 2008, when University of Minnesota researchers created a beating rat heart in the lab. In a June 13 paper in Nature Medicine, scientists from Massachusetts General Hospital and elsewhere described how they had used the method to create a rat liver.

Lung diseases, such as cystic fibrosis and cancer, kill 400,000 people in the U.S. each year. But regenerating lung tissue is hard. Today, the only option is to transplant an entire lung obtained from a cadaver. Fewer than 20% of patients who have a lung transplant are still alive after 10 years.

Laura Niklason, a professor at Yale, and lead author of the latest Science paper, tried an alternative approach in rats. The idea is to strip down a lung to its basic infrastructure, then repopulate it with lab-grown cells.

A lung is complex. Alan Russell, director of the McGowan Institute for Regenerative Medicine, likens it to a big city: If skyscrapers are equivalent to cells, then a city's underlying infrastructure -- roads, sewers, phone lines and electrical cabling -- are akin to a lung's 'extracellular matrix.'

This matrix sends out biological signals, attracting cells to the right locations and helping them to function in the right way, says Dr. Russell, who wasn't involved in the study.

Dr. Niklason and her colleagues first used a mild detergent to dissolve all the cells contained in the lungs of dead adult rats. Left behind were the underlying structures of the airways and vascular system, plus the matrix, which is made of collagen and other proteins.

The Yale researchers suspended the matrix in a glass jar. Lung cells taken from rat fetuses were injected into the setup, along with nutrients that helped the cells grow. Within days, the matrix had done its magic. The fetal cells repopulated the matrix. 'It looked like a lung, it was pink and it had the same shape,' said Dr. Niklason.

But could it function as that complex organ, whose thousands of branching airways contain millions of air sacs that exchange oxygen and carbon dioxide? As a test, the researchers cut out one lung in each of four adult rats and replaced them with their lab-grown versions.

The results were encouraging. For 45 to 120 minutes, the engineered lungs exchanged oxygen and CO2 at 95% of the efficiency of natural lungs. Longer term, scientists will have to regenerate entire lungs in larger animals before trying it in people.

科学家在实验室中成功再造了鼠肺，在制造人体器官用于移植和疾病治疗的道路上迈出了重要的一小步。

由耶鲁大学研究人员牵头的一个小组分离了老鼠的肺脏，用新的细胞在玻璃瓶中再造了鼠肺。在移植到活鼠体内几小时后，新的肺脏成功实现了氧气和二氧化碳的交换，就像天然肺脏一样。研究结果发表在《科学》(Science)杂志网络版上。

该研究由耶鲁大学和美国国立卫生研究院(National Institutes of Health)提供资金。研究建立于近年来数项具有突破性的试验的基础上。2008年，同一技术的应用实现了突破性进展，当时明尼苏达大学的研究人员在实验室中再造了一个可以跳动的老鼠心脏。在《自然医学》(Nature Medicine) 6月13日发表的文章中，马萨诸塞综合医院(Massachusetts General Hospital)等地的科学家描述了如何用这一方法再造了老鼠肝脏。

在美国，囊肿性纤维化症和肺癌等肺部疾病每年会造成40万人死亡。不过，再造肺部组织是困难的。目前，唯一的选择是从尸体上移植整个肺脏。肺移植病人的10年存活率不到20%。

耶鲁大学教授、《科学》杂志上最新文章的主笔尼可拉森(Laura Niklason)则在老鼠身上尝试了另外一种方法。他的想法是把肺脏分解至最基本的结构，然后用实验室培养的细胞再造鼠肺。

肺脏结构复杂。麦高恩再生医学研究所(McGowan Institute for Regenerative Medicine)主任罗素(Alan Russell)把肺脏比作一个大城市：如果把高楼大厦比作细胞的话，那么城市的基础设施──公路、下水道、电话线和电线──就像是肺的细胞外基质。

罗素说，细胞外基质发出生物信号，把细胞吸引到正确的位置，帮助它们以正确的方式发挥作用。罗素没有参与这项研究。

尼可拉森及其同事首先用一种温和的洗涤剂分解了死亡成年老鼠的全部肺细胞。剩下的是气管和血管系统的基本机构，还有由胶原蛋白和其他蛋白质构成的细胞外基质。

耶鲁大学研究人员将基质悬浮在一个玻璃瓶中。从胎鼠中取出的肺细胞被注入这个装置系统中，同时还有帮助细胞生长的营养物质。几天内，基质发挥了魔力。胎鼠细胞重新充斥了基质。尼可拉森说，看起来就像一个肺脏，粉红色的，形状也一样。

不过，它能够和结构复杂的天然肺脏一样发挥作用吗？毕竟天然肺脏的数千个气管分支中含有数百万个气囊，负责进行氧气和二氧化碳的交换。在试验中，研究人员在四只成年老鼠身上各切下一个肺脏，用实验室再造的肺脏取而代之。

试验结果令人鼓舞。在45到120分钟里，再造的肺脏交换氧气和二氧化碳的效率是天然肺脏的95%。长期来看，科学家们将必须再造更大型动物的整个肺脏，之后才能进行人体试验。