29 August 2013

Scientists have grown a model of the human brain "in vitro"

The cells self-organized into the brain
Scientists have repeated the development of the human brain in a Petri dishNadezhda Markina, <url>

To grow a model of the human brain in vitro is the dream of neurophysiologists.

Most diseases of the human brain do not lend themselves well to imitation on animal models — the governing organ of our body is too complex. Now this dream has become a reality: a team of researchers from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna, the University of Edinburgh and St. George's University in London has grown such a model — a mini human brain. They described the details of the experiment in the journal Nature (Madeline A. Lancaster et al., Cerebral organoids model human brain development and microcephaly – VM).

Madeline Lancaster and her colleagues used induced pluripotent stem cells (iPSCs) as a basis, which they obtained using a standard technique from human skin fibroblasts. But in their work, scientists have demonstrated that iPSCs can become a source not only of a variety of cells and tissues, but also of an entire organ, even the most complex.

First, the researchers turned iPSCs into neuronal cells in a Petri dish by treating them with growth factors, then placed groups of these cells in a special gel and finally grew the structure in a bioreactor.

And they turned out, no less, a rudimentary human brain — a mini-brain the size of a peanut grain. Scientists call it a "brain organoid". Having reached 4 mm, it was preserved for 10 months in a bioreactor with a special nutrient medium.

Surprisingly, the organoid really repeats the development of the human brain in the embryo. It is similar in shape to the embryonic brain, its outer layer resembles the forming cortex of the brain, and the internal structure is very similar to the structure of the human brain in the early stages.

Fluid-filled cavities resembling the ventricles of the brain appeared in the organoid. And something resembling a choroid plexus (vascular plexus of the ventricles of the brain, producing cerebrospinal fluid) appeared on their surface.

Histological analysis showed that the organoid consists of different parts. And different parts of it produced biochemical markers characteristic of human brain structures, the researchers write. For example, they observed in the organoid the rudiment of the hippocampus. The mini-brain has formed a complex cellular architecture characteristic of the developing cortex, with the allocation of several morphologically different cellular layers.

Moreover, even retinal tissue has formed on the surface of the brain organoid (it is shown in brown in the picture).

Scientists have registered that cells of different layers interact with each other — the same thing happens during the development of the brain in the embryo. Some cell populations migrate to a new place of residence, in accordance with the role they have to perform.

The model is based on the idea that the development of nerve cells from pluripotent stem cells follows the same program as the development of the brain in the embryo. This idea has been discussed for the last five years. Different groups of scientists managed to show how neuronal stem cells in a Petri dish form connections characteristic of the architecture of the human cerebral cortex.

"Lancaster and his colleagues have taken these achievements to a new level. They obtained a whole rudimentary brain and demonstrated how accurately self—organizing cells repeat the features of brain development in the embryo," Oliver Brustle, a neurophysiologist from the University of Bonn, Germany, writes in the journal Nature (Oliver Brustle, Developmental neuroscience: Miniature human brains – VM).

Such a mini-brain is not a toy for biologists at all. It can serve as an authentic model for studying human brain development disorders and simulating neurodegenerative diseases.

Of course, the shape and structure of its individual parts only resemble different areas of the brain. And since the organoid is deprived of blood supply, the metabolism of its constituent cells is limited. Moreover, there are "dead zones" in it, which lack oxygen and nutrition.

But even with these limitations, such a brain model has huge potential, writes Oliver Brustle. It will give an opportunity to study the development of the human brain, changing the conditions of its cultivation, depending on the composition of the environment. Accordingly, it will be possible to simulate what conditions will lead to certain disorders of the development of the cortex and other brain structures.

The authors of the model have already made an important practical step. They grew a brain organoid from iPSCs obtained from a patient with a hereditary form of microcephaly and compared it with a normal mini-brain.

In the pathological organoid, they found fewer progenitor cells and an increased number of differentiated neurons. Paradoxically, such premature maturation may be a mechanism leading to microcephaly, scientists believe.

Portal "Eternal youth" http://vechnayamolodost.ru29.08.2013

Found a typo? Select it and press ctrl + enter Print version