Scientists have grown ‘mini brains’ from stem cells. Then, brains as developed eyes. : ScienceAlert

Mini brains grown in the lab from stem cells spontaneously developed rudimentary eye structures, scientists reported 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 will help us to 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 neuroscientist Jay Gopalakrishnan of the University Hospital Düsseldorf in Germany.

“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.”

A close-up view of a beige blob (brain organoid) with two dark dots that are the rudimentary eyes. (Elke 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 into 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 in 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 wrote in their 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 do not attempt to force the development of purely neuronal cells in the early stages of neuronal differentiation and add retinol acetate to the culture medium as an aid to eye development.

development
(Gabriel et al., cell stem cells, 2021)

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 embryo, meaning these organelles could 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,” said Gopalakrishnan.

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 wrote in their paper.

“We believe in it [these] are next-generation organelles helping to 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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