Growing model brains: An embryonic idea

A group of stem-cell biologists have grown an “organoid” that resembles a brain

REGENERATIVE medicine, the science of producing tissues and organs from stem cells, is a rapidly developing field.

This week, however, it took a leap forward that was big even by its own demanding standards. A team of researchers led by Madeline Lancaster of the Austrian Academy of Sciences, in Vienna, announced that they have grown things which, while not human brains, resemble brains in important ways.

Dr Lancaster’s organoids, as she calls them, are a far cry from the brains in jars beloved of the writers of horror movies. But they do contain several recognisably different types of nerve cell and have anatomical features which look like those of real brains. They might be used to study, in ways that would be unethical in a living human being or impossible even in a mouse, the crucial early stages of brain development, and how they can go wrong. They could be employed to test drugs in ways that mere cell cultures cannot be. And because they can be made, if needed, from the cells of living people, they might even illuminate the particular problems of individual patients.

To make an organoid, Dr Lancaster’s team start, as they describe in an article in Nature, with what is known as an embryoid body. Just as an organoid has some features of an organ without truly being one, so an embryoid body has some features of an embryo without actually being one. Embryoid bodies can be grown either from natural stem cells—themselves derived ultimately from real embryos—or from what are known as induced pluripotent cells, which are made from adult cells (usually skin cells) that have been treated with four crucial biochemical factors which cause them to forget their identity and behave like embryonic cells.

Embryos have three layers: endoderm, mesoderm and ectoderm. Each turns into an eclectic mixture of body parts in the complete organism. Nervous systems grow from the ectoderm (which also contributes dental enamel and the skin’s epidermis, among other things), so the team put ectodermal cells into droplets of gel and then floated the droplets in a nutrient broth in a gently rotating bioreactor (which allowed the cells to grow without being shaped by the constraint of a vessel such as a Petri dish) to see what would happen.

Though the result (pictured above) may not look much like a brain to a layman, to an expert the resemblance is remarkable. After ten days the organoid has developed neurons. After 30 days it has regions recognisably similar to some of those in a real brain. And though, because they lack the blood supply of a real brain, organoids never grow much bigger than 4mm across, they live a long time. Some are now a year old and still going strong.

Real brains consist in large measure of layers of neurons called the cortex. This surrounds fluid-filled spaces known as ventricles. That is more or less the anatomy of an organoid. Many of them also contain areas which look like choroid plexuses. These are places that absorb nutrients from the bloodstream and dump waste into it. They also generate the cerebrospinal fluid that fills ventricles.

Signs of other structures turn up too. The various lobes of a real brain sport different mixtures of neurons. The team see signs of this in the organoids. They found evidence of retinas (the back of the eye is an outgrowth of the brain), of meninges (the membranes that surround the brain) and of hippocampal cells (the hippocampus is a part of the brain which is crucial for memory formation). The organoids, then, look as though they are making a fair fist of trying to become real brains.

So the method clearly works.

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