SCIENCE: 20.12.2013

In research that Science's editors chose as a runner-up for Breakthrough of the Year, scientists coaxed cells called pluripotent stem cells to grow into tiny "organoids"—liver buds, mini-kidneys, and even rudimentary human brains—in the lab.

Left alone in a lab dish, pluripotent stem cells run riot. They differentiate into a disorganized mass of tissues: beating heart cells, neurons, even hair and teeth. It's still a challenge to coax stem cells to grow into specific tissues, let alone into organized structures. This year, researchers did just that, in spectacular style, growing a variety of "organoids" in the lab: liver buds, mini-kidneys, and, most remarkably, rudimentary human brains.

The brains, grown by Austrian researchers, differ in important ways from the real thing. Because they have no blood supply, they stop growing once they reach the size of an apple seed. Cells at the core, starved of oxygen and other nutrients, die off. But the organoids mimic developing human brains to a surprising degree, developing eye tissue and layers that, under the microscope, resemble those in the brain of an early human fetus.

Inspired by previous work that had grown mini-guts from stem cells, the researchers began by encouraging human embryonic stem cells and induced pluripotent stem (iPS) cells to become neural stem cells. Then they suspended clumps of the cells in a gelatinous material called Matrigel and let them grow in a bioreactor, which rotates to help nutrients reach the cell clusters.

To the scientists' surprise, after a few weeks they saw darker pigmented cells that seemed to resemble early eye development. On closer inspection, they found evidence that the organoids had developed layers identifiable as forebrain, midbrain, and hindbrain, all typical of fetal brains. They also saw evidence for an outer subventricular zone, which is present in human brains but not mouse ones.

The mini-brains have already yielded insights into microcephaly, a condition in which the brain doesn't grow to its full size. When the team started with iPS cells derived from a microcephaly patient, the resulting organoids were smaller than normal because stem cells stopped dividing too soon. With further development, researchers hope to use the mini-brain technique to investigate other brain diseases.

http://www.sciencemag.org/content/342/6165/1436.2.full