Scientists grew ‘mini-brains’ from stem cells, then the brains kind of grew eyes: ScienceAlert

Mini-brains grown in the lab from stem cells spontaneously developed rudimentary eye structures, scientists reported in a fascinating 2021 paper.

On tiny human brain organoids cultured in dishes, two optical sections with bilateral symmetry were observed, reflecting the development of eye structures in human embryos. This incredible result could help us better understand the process of eye differentiation and development, as well as eye diseases.

“Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are sensitive to light and harbor cell types similar to those found in the body,” said neuroscientist Jay Gopalakrishnan of University Hospital. from Düsseldorf in Germany in a 2021 statement.

“These organoids can help study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies.”

Close-up view of a beige blob (the organoid of the brain) with two dark dots which are the rudimentary eyes
(Elke Gabriel)

Brain organoids aren’t real brains, as you might think. They are small, three-dimensional structures developed from induced pluripotent stem cells – cells harvested from adult humans and transformed into stem cells, which have the potential to grow into many different tissue types.

In this case, these stem cells are tricked into growing into masses of brain tissue, with nothing resembling thoughts, emotions, or consciousness. These “mini brains” are used for research purposes where using actual living brains would be impossible, or at the very least, ethically tricky – testing responses to drugs, for example, or observing development. cell under certain unfavorable conditions.

This time, Gopalakrishnan and his colleagues were looking to observe the development of the eyes.

In previous research, other scientists had used embryonic stem cells to grow optic cups, the structures that grow throughout almost the entire eyeball during embryonic development. And other research had developed cup-shaped optical structures from induced pluripotent stem cells.

Rather than developing these structures directly, Gopalakrishnan’s team wanted to see if they could be developed as integral parts of brain organoids. This would add the benefit of seeing how the two tissue types can grow together, rather than just developing optical structures in isolation.

“Eye development is a complex process, and understanding it may help to elucidate the molecular basis of early retinal disease,” the researchers write in their paper.

“Thus, it is crucial to study the optic vesicles which are the outline of the eye whose proximal end is attached to the forebrain, essential for the proper formation of the eye.”

Previous work on the development of organoids showed evidence of retinal cells, but these did not develop optical structures. So the team changed their protocols.

They did not attempt to force the development of purely neural cells in the early stages of neural differentiation and added retinol acetate to the culture medium to promote eye development.

An illustration showing the development of an organoid.
(Gabriel et al., Cell Stem Cell2021)

Their carefully tended baby brains formed optic cupules as early as 30 days of development, with the structures clearly visible at 50 days. This is consistent with the timing of eye development in the human embryo, meaning that these organoids could be useful for studying the intricacies of this process.

There are also other implications. The optic cups contained different types of retinal cells, which organized themselves into neural networks that reacted to light, and even contained lens and corneal tissue. Finally, the structures displayed retinal connectivity to regions of brain tissue.

“In the mammalian brain, nerve fibers from retinal ganglion cells connect to their brain targets, something that has never been demonstrated before in an in vitro system,” Gopalakrishnan said.

And it’s reproducible. Of the 314 brain organoids the team developed, 73% developed optic cupules. The team hopes to develop strategies to keep these structures viable over longer timescales to perform further research with huge potential, the researchers said.

“Brain organoids containing optic vesicles displaying highly specialized neural cell types can be developed, paving the way for the generation of personalized organoids and retinal pigment epithelial sheets for transplantation,” they wrote in their paper.

“We believe that [these] are next-generation organoids helping to model retinopathies that emerge from early neurodevelopmental disorders.”

The research has been published in Cell Stem Cell.

A version of this article was first published in August 2021.

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