German Scientists at Düsseldorf University Hospital have created a primitive mini-brain that can perceive light!
Brain organoids. Image Courtesy of Gabriel et al., Cell Stem Cell
Pluripotent stem cells can differentiate into any cell type. They occur naturally in the embryo and in some adult organs and tissues.
In the hands of scientists, these pluripotent stem cells, also known as iPSCs, are valuable allies when studying the development of organs or diseases. When grown under the right conditions, they form organoids. Unlike conventional cell cultures, which consist of single-layered mats, organoids grow in three dimensions and mimic the organization of organ tissues.
Scientists at Düsseldorf University Hospital have created a particularly complex organoid – a primitive mini-brain with two functional optic vesicles.
From cell to organ
It all starts with iPSCs. To get them, you need to genetically reprogram adult, differentiated donor cells. They revert to an embryonic state and can again differentiate into any cell type. In the case of this experiment, scientists programmed them to become small, primitive brains.
The cells transformed and rearranged themselves in the same way as during embryogenesis. After 10 days in culture, they formed a neurosphere. After 30 days, the organoid becomes more complex, and non-neuronal cells appear: two rather rudimentary optic vesicles at the front of the organoid. These ‘eyes’ come from the outer cell layer. After 60 days, two lens-like structures and a cornea-like epithelial layer appeared in the optic vesicles.
Light-sensitive mini-brains
The transcriptomic activity of the vesicles suggests that they have a retina and appear to be connected to the organoid neuronal cells. German scientists, therefore, decided to test their sensitivity to light. Using electroretinography, they were able to observe the electrical response to light stimuli, suggesting that the immature optic vesicles perceive light.
“Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are sensitive to light and contain cell types similar to those of the body,” explains Jay Gopalakrishnan from the University Hospital Düsseldorf.
His team created 314 brain organoids, 72 of which developed optical vesicles. The technique is thus reproducible and could speed up research into brain development or hereditary eye diseases.
“These organoids can be used to study eye-brain interactions during embryonic development, as a model for inherited retinal diseases, and to generate patient-specific retinal cells for personalized therapy,” concludes Jay Gopalakrishnan.
References
Gabriel, E., Albanna, W., Pasquini, G., Ramani, A., Josipovic, N., Mariappan, A., Schinzel, F., Karch, C. M., Bao, G., Gottardo, M., Suren, A. A., Hescheler, J., Nagel-Wolfrum, K., Persico, V., Rizzoli, S. O., Altmüller, J., Riparbelli, M. G., Callaini, G., Goureau, O., Papantonis, A., … Gopalakrishnan, J. (2021). Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell, 28(10), 1740–1757.e8. https://doi.org/10.1016/j.stem.2021.07.010
