The bizarre for basic research: Researchers have grown so-called brain organoids from induced stem cells, which form visual shells. These structures have basic elements of the eyes, respond to light and are connected to the nervous system of the brain-like cell clump. The new complex organoids help to research development processes and retinal diseases and could provide tissue for personalized drug tests or transplants, the scientists explain.
The brain, eyes and other types of tissue – how do these complex structures in our body arise and function? For some time now, a new technology has been available to science to gain insights into these questions “in the test tube”. To do this, researchers use so-called induced pluripotent stem cells (iPSCs) – body cells that have been reprogrammed in such a way that they fall back into the undifferentiated state and can develop again into different types of tissue. Certain techniques can then be used to stimulate the iPSCs to develop three-dimensional collections of cells in nutrient media that have the characteristics of certain body structures – organoids.
Two-component oganoids
Versions of these structures have already been created, which consist of nerve cells and produce basic structures and features that are similar to those of the brain. These brain organoids are used to study neural development processes and the causes of cerebral diseases. Researchers have also used the organoid system to simulate different structures of the visual system in the laboratory. For example, they were able to create the optic nerve cap that forms the retina – the light-sensitive layer of tissue on the back of the eye. It has also already been possible to stimulate iPSCs to produce structures similar to tendons.
The scientists led by Jay Gopalakrishnan from the Heinrich Heine University in Düsseldorf have now succeeded in uniting brain tissue and visual structures in an organoid system. This is therefore similar to the natural model of the body, in which these two elements are closely linked. For their method, the researchers modified a protocol that they had previously developed for the conversion of human iPSCs into neuronal tissue. As they report, they achieved their goal by adding a substance that is known to be involved in eye development: When they added retinol acetate to the nutrient medium at a special stage of the differentiation of the cell clump, eye-specific structures were formed.
Photosensitive and wired
After 30 days, the genesis of the paired optical cups became apparent in the brain organoids and within 50 days they matured. This time frame also corresponds to the retinal development in the human embryo, the researchers explain. “Our work underscores the remarkable ability of brain organoids to create primitive sensory structures that are sensitive to light and harbor cell types that are similar to those in the body,” says Gopalakrishnan. As the studies showed, the structures contained different types of cells in the retina that formed electrically active neural networks that also responded to light.
The optic brain organoids also contained lens and corneal tissue and had a connection between the retina and certain regions of the brain organoid, the team reports. “In the mammalian brain, the nerve fibers of the retinal ganglion cells stretch to connect to their targets in the brain, an aspect that has never been demonstrated in an in vitro system,” says Gopalakrishnan. In addition, the production method for these organoids is relatively effective and is therefore suitable for use as a new model system for science: 72 percent of the 314 iPSC structures generated for the study turned into optic brain organoids, the scientists report.
Now they are working on further optimizing the procedure in order to keep the optic nerve heads viable for long periods of time, as well as on strategies to be able to use them for examinations. “These organoids could help study the interactions between the brain and the eye during embryonic development, model congenital retinal diseases and create patient-specific retinal cell types for personalized drug testing and transplant therapies,” says Gopalakrishnan.
Source: Heinrich Heine University Düsseldorf, specialist article: Cell Stem Cell, doi: 10.1016 / j.stem.2021.07.010