Scientists Grow Stem Cell ‘Mini Brains’, Then Brains Grow Some Advanced Eyes : ScienceAlert

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

In miniature, human-derived brain organoids grown in dishes, two bilaterally symmetrical optic cups were shown to develop, mirroring 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 organelles to create primitive sensory structures that are sensitive to light and harbor cell types similar to those found in the body,” neuroscientist Jay Gopalakrishnan of the University Hospital Düsseldorf in Germany said in a statement of 2021.

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

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

Brain organoids are not real brains, as you might think. They are small, three-dimensional structures grown from induced pluripotent stem cells – cells harvested from adult humans that have been transformed into stem cells, which have the potential to develop into many different types of tissues.

In this case, these stem cells are induced to grow into blobs of brain tissue, with nothing resembling thoughts, feelings or consciousness. Such “mini-brains” are used for research purposes where using actual living brains would be impossible, or at least, ethically difficult – testing responses to drugs, for example, or observing cell growth under certain adverse conditions.

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

In previous research, other scientists had used embryonic stem cells to grow optic cups, the structures that grow over nearly the entire eyeball during embryonic development. And other research had 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 integral part of brain organoids. This would add the advantage of seeing how the two tissue types can grow together, rather than just growing optical structures in isolation.

“Eye development is a complex process, and understanding it could allow support for the molecular basis of early retinal diseases,” the researchers wrote in their paper.

“Thus, it is important to study the optic vesicles which are the progenitor of the eye whose proximal end is connected to the forebrain, necessary for proper eye formation.”

Previous work on developing organelles showed evidence of retinal cells, but these did not develop visual structures, so the team changed their protocols.

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

An illustration showing the development of an organelle.
(Gabriel et al., Cell stem cell2021)

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

There are other consequences. The optic cups contained different types of retinal cells, which were organized into light-responsive neuronal networks and even contained lens and corneal tissue. Finally, the structures showed connectivity of the retina with areas of brain tissue.

“In the mammalian brain, nerve fibers of retinal ganglion cells extend to connect to their brain targets, an aspect that has never been demonstrated before 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 perform more in-depth research with enormous potential, the researchers said.

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

“We believe that [these] are next-generation organoids that help model retinopathies resulting 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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