迷你器官的研究进展——大脑

2015/8/14 10:08:42 本站原创 佚名 【字体:

廖联明   编译

 

生物学家们正在培育一系列“类器官”,并借此研究人类发育的调控。

 

当维也纳分子生物技术研究所的博士后Madeline Lancaster 意识到她已经意外地培育了一个大脑时,注定了这是201111月的不寻常的一天。数周来,她一直在尝试着将人类胚胎干细胞分化成神经丛,神经丛是一群能够进一步发育成多种不同类型的神经元的细胞簇。但由于某些原因,那些胚胎干细胞无法黏附在培养皿底部,它们反而悬浮起来,形成异常的形状,看上去好像乳白色的球体。

 “我真的不知道这些球体是什么东西”,Lancaster说。她在其中的一个球体上发现了一粒奇怪的色素点。当将它置于显微镜下观察时,她意识到这个色素点是视网膜发育过程中出现的暗细胞,也是大脑发育的产物。当她切开其中一个球体时,在里面找到了各种各样的神经元。Lancaster意识到,这些细胞就像胚胎的大脑一样,已经准确无误地自行聚集.然后她直接告诉她的导师——干细胞生物学家 Jürgen Knoblich这个消息。“我发现了一些令人惊讶的东西,你必须跟我去看看。”她跟导师说。

Lancaster和她的同事们并非第一个在培养皿上培育大脑的研究者。2008年,日本的研究人员报告说,他们已经促使小鼠和人类的胚胎干细胞分化成分层的小球,这让人联想到了大脑皮层。从那时起,生物学界便开始了将干细胞培育成基本器官的研究。通过小心地利用特定时间的化学信号,世界各地的研究人员已经培育出眼睛、肠道、肝脏、肾脏、胰腺、前列腺、肺、胃和乳房等的类组织的三维结构。这部分组织之所以被称为“类器官”,是因为它们能够模拟真实器官的一些构造和功能,可作为疾病模型和药物筛选平台,并且最终可能用于修复受损的器官,而且加深了我们对人体发育的了解。“这可能是最近56年来,干细胞领域的最重要的发展”,维尔康基金会及英国剑桥大学MRC干细胞研究所的主任Austin Smith说。

目前,“类器官”的产品还不够完善。有些类器官缺少一些重要的细胞,其他只能模拟器官发育最早期的结构与功能或者不同批次的类器官的结构与功能有差异。因此研究人员正努力改善类器官的质量,使得它们更加复杂、成熟和更有可重现性。不过,生物学家们感到十分惊讶的是如此微小的信号刺激即可诱导细胞自我组合成复杂的结构。

 

The boom in mini stomachs, brains, breasts, kidneys and more

Biologists are building banks of 'organoids', and learning a lot about human development on the way.

It was an otherwise normal day in November when Madeline Lancaster realized that she had accidentally grown a brain. For weeks, she had been trying to get human embryonic stem cells to form neural rosettes, clusters of cells that can become many different types of neuron. But for some reason her cells refused to stick to the bottom of the culture plate. Instead they floated, forming strange, milky-looking spheres.

 

I didn't really know what they were,” says Lancaster, who was then a postdoc at the Institute of Molecular Biotechnology in Vienna. That day in 2011, however, she spotted an odd dot of pigment in one of her spheres. Looking under the microscope, she realized that it was the dark cells of a developing retina, an outgrowth of the developing brain. And when she sliced one of the balls open, she could pick out a variety of neurons. Lancaster realized that the cells had assembled themselves into something unmistakably like an embryonic brain, and she went straight to her adviser, stem-cell biologist Jürgen Knoblich, with the news. “I've got something amazing,” she told him. “You've got to see it.”

 

Lancaster and her colleagues were not the first to grow a brain in a dish. In 2008, researchers in Japan reported that they had prompted embryonic stem cells from mice and humans to form layered balls reminiscent of a cerebral cortex. Since then, efforts to grow stem cells into rudimentary organs have taken off. Using carefully timed chemical cues, researchers around the world have produced three-dimensional structures that resemble tissue from the eye, gut, liver, kidney, pancreas, prostate, lung, stomach and breast. These bits of tissue, called organoids because they mimic some of the structure and function of real organs, are furthering knowledge of human development, serving as disease models and drug-screening platforms, and might eventually be used to rescue damaged organs. “It's probably the most significant development in the stem-cell field in the last five or six years,” says Austin Smith, director of the Wellcome Trust/MRC Stem Cell Institute at the University of Cambridge, UK.

 

The current crop of organoids isn't perfect. Some lack key cell types; others imitate only the earliest stages of organ development or vary from batch to batch. So researchers are toiling to refine their organoids — to make them more complex, more mature and more reproducible. Still, biologists have been amazed at how little encouragement cells need to self-assemble into elaborate structures.

来源:

Nature 523, 520–522 (30 July 2015) doi:10.1038/523520a

 

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