Brain organoids develop optic cups that respond to light

Date:
August 17, 2021
Source:
Cell Press
Summary:
Human induced pluripotent stem cells (iPSCs) can be used to generate
brain organoids containing an eye structure called the optic cup,
according to a new study. The organoids spontaneously developed
bilaterally symmetric optic cups from the front of the brain-like
region, demonstrating the intrinsic self-patterning ability of
iPSCs in a highly complex biological process.



FULL STORY ========================================================================== Human induced pluripotent stem cells (iPSCs) can be used to generate brain organoids containing an eye structure called the optic cup, according to
a study published August 17 in the journal Cell Stem Cell. The organoids spontaneously developed bilaterally symmetric optic cups from the front
of the brain-like region, demonstrating the intrinsic self-patterning
ability of iPSCs in a highly complex biological process.


==========================================================================
"Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell
types similar to those found in the body," says senior study author Jay Gopalakrishnan of University Hospital Du?sseldorf. "These organoids can
help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal
cell types for personalized drug testing and transplantation therapies."
Many aspects of human brain development and diseases can be studied using
3D brain organoids derived from pluripotent stem cells, which can give
rise to all cell types in the body. Researchers previously used human
embryonic stem cells to generate the optic cup, which gives rise to
the retina -- the light- sensitive layer of tissue at the back of the
eye. Another study demonstrated that optic-cup-like structures can be
generated from iPSCs, which are derived from adult cells that have been genetically reprogrammed back into an embryonic-like pluripotent state.

In the past, the production of optic cups from pluripotent stem cells
focused on generating the pure retina. Until now, optic cups and other
3D retinal structures had not been functionally integrated into brain organoids.

To achieve this feat, Gopalakrishnan and his team modified a protocol
they previously developed for turning iPSCs into neural tissue. The
human brain organoids formed optic cups, which appeared as early as 30
days and matured as visible structures within 50 days. This time frame parallels that of retinal development in the human embryo and could make certain types of developmental neurobiology experiments more efficient.

Across 16 independent batches from four iPSC donors, the researchers
generated 314 brain organoids, 72% of which formed optic cups, showing
that the method is reproducible. These structures contained diverse
retinal cell types, which formed electrically active neuronal networks
that responded to light. The optic cup brain organoids also contained
lens and corneal tissue and exhibited retinal connectivity to brain
regions. "In the mammalian brain, nerve fibers of retinal ganglion cells
reach out to connect with their brain targets, an aspect that has never
before been shown in an in vitro system," Gopalakrishnan says.

In future studies, they plan to develop strategies to keep the optic
cups viable for long time periods, using them to investigate mechanisms
that cause retinal disorders.

========================================================================== Story Source: Materials provided by Cell_Press. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasa
Josipovic, Aruljothi Mariappan, Friedrich Schinzel, Celeste
M. Karch, Guobin Bao, Marco Gottardo, Ata Alp Suren, Ju"rgen
Hescheler, Kerstin Nagel-Wolfrum, Veronica Persico, Silvio
O. Rizzoli, Janine Altmu"ller, Maria Giovanna Riparbelli, Giuliano
Callaini, Olivier Goureau, Argyris Papantonis, Volker Busskamp,
Toni Schneider, Jay Gopalakrishnan. Human brain organoids assemble
functionally integrated bilateral optic vesicles. Cell Stem Cell,
2021; DOI: 10.1016/j.stem.2021.07.010 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210817111359.htm

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