nature | 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 reported1
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 (see ‘The organoid bank’).
“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. “It doesn't require any super-sophisticated bioengineering,”
says Knoblich. “We just let the cells do what they want to do, and they
make a brain.”
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