Scientists grew ‘mini brains’ from stem cells and then the brains developed what looked like advanced eyes: ScienceAlert

Scientists grew ‘mini brains’ from stem cells and then the brains developed what looked like advanced eyes: ScienceAlert

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Lab-grown mini brains from stem cells spontaneously developed rudimentary eye structures, scientists report in a fascinating 2021 paper.

On small human-derived brain organoids grown in dishes, two bilaterally symmetrical optic cups are seen growing, mirroring the development of eye structures in human embryos. This amazing result may help us better understand the process of eye differentiation and development, as well as eye diseases.

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

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

(Every Gabriel)

Brain organoids are not real brains, as you might think of them. They are tiny, three-dimensional structures grown from induced pluripotent stem cells—cells harvested from elderly people and engineered back into stem cells that have the potential to grow into many different types of tissue.

In this case, these stem cells are forced to grow in patches of brain tissue with nothing resembling thoughts, emotions or consciousness. Such “mini-brains” are used for research purposes where the use of actual living brains would be impossible or at least ethically difficult – testing drug responses, for example, or monitoring cell development under certain adverse conditions.

This time, Gopalakrishnan and his colleagues aimed to observe eye development.

In previous research, other scientists have used embryonic stem cells to grow optic cups, the structures that develop into almost the entire eyeball during embryonic development. And other research has developed optical cup-like structures from induced pluripotent stem cells.

Instead of growing these structures directly, Gopalakrishnan’s team wanted to see if they could be grown as an integrated part of brain organoids. This would add the benefit of seeing how the two types of tissue can grow together, rather than simply growing optical structures in isolation.

“Eye development is a complex process and understanding it may allow to support the molecular basis of early retinal diseases,” the researchers writes in his paper.

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

Previous work developing organoids showed evidence of retinal cells, but they did not develop optical structures, so the team changed their protocols.

They did not try to force the development of purely neuronal cells in the early stages of neuronal differentiation and added retinol acetate to the culture medium as an aid to eye development.

Scientists grew ‘mini brains’ from stem cells and then the brains developed what looked like advanced eyes: ScienceAlert
(Gabriel et al., Cellular stem cell2021)

Their carefully tended baby brains had formed optic cups as early as 30 days of development, with structures clearly visible at 50 days. This is consistent with the timing of eye development in the human embryomeaning that these organelles can be useful for studying the intricacies of this process.

There are other implications as well. The optic cups contained different types of retinal cells that organized themselves into neural networks that responded to light, and even contained lens and corneal tissue. Finally, the structures show connectivity of the retina with regions of brain tissue.

“In the mammalian brain, retinal ganglion cell nerve fibers reach out to connect to their brain targets, an aspect that has never before been shown in an in vitro system.” Gopalakrishnan said.

And it’s reproducible. Of the 314 brain organoids the team grew, 73 percent developed optic cups. The team hopes to develop strategies to keep these structures viable over longer time scales to carry out more in-depth research with huge potential, the researchers said.

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

“We believe in it [these] are next-generation organelles to help model retinopathies that arise from early neurodevelopmental disorders.”

The study was published in Cellular stem cell.

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

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