Sometimes a paper really catches your eye like a new Cell Stem Cell pub reporting eye-like structures grown on brain organoids.
Let’s take a quick look at this paper, its context, and the potential big-picture implications.
Brain organoids with “eyes”?
At first glance, I thought they grew the brain organoids and the “eyes” separately and then grafted the eyes onto the brain organoids or had taken an “assembloid” approach.
But no. It seems they were able to generate primordial eye like structures right there within the brain organoids.
It’s possible to grow retinal organoids so since it is, of course, also possible to grow brain organoids (and some cortical organoids even have some retina features), maybe we shouldn’t be so surprised that a method can be devised that bridges such protocols and you get both all in one?
Here’s the key passage from the paper:
Brain organoids to assemble functionally integrated optic vesicles allowing inter-organ interactions occurring within a single organoid has not yet been demonstrated. One possibility to generate such hybrid organoids in vitro is to fuse distinct cellular origin components of brain and optic vesicles via the recently described “assembloid” approach (Andersen et al., 2020). Interestingly, cerebral organoids could display an immature retina-like structure (Lancaster et al., 2013). We thus modified the culture conditions and generated human brain organoids with bilaterally symmetric optic vesicles, containing neuronal and non-neuronal cell types and exhibiting functional circuitry. We could generate these organoids within 60 days, a time frame that seemingly parallels human embryonic retina development.
The bilateral symmetry is striking as you can see in the image above. It might be odd to think of brains with eyes nestled right in the tissue. In a sense though the eyes, especially the retinas, are just extensions of the brain as parts of the CNS.
More than just retina
This team did a large amount of work for their paper including staining, transcriptomics assays, and more. Another striking conclusion was that the structures on the organoids weren’t just retina. They found evidence of additional eye cell type transcriptomic signatures including for lens and cornea.
Further, they report functional connectivity between the cortical tissue and the eye-like structures. They also present evidence that the structures have light-sensing capability. While this has been reported previously for retinal organoids, it’s impressive for this interorgan system to have that ability.
The authors do note some limitations to their work:
“Although the OVB-organoids can generate various neuronal, non-neuronal, and retinal cell types, a significant limitation is that the viability of the organoids beyond day 60 is questionable. As a result, OVB-organoids cannot generate mature retinal cell types, posing the question of designing strategies that can allow culturing them for a longer time. Another limitation is the consistency of OBV-organoids to generate bilateral optic vesicles across several iPSCs donors.”
So we don’t know how long these kinds of organoids can be grown and it’s not clear how well this method will work across diverse iPS cell donors. These are important considerations.
Impact and implications
Still, it’s easy to imagine future impact from a paper like this and other similar work on retinal organoids.
While studying retinal organoids is exciting and powerful, what if you can routinely study a model version of the developing human retina that is attached to the developing brain? This may open new doors and provide unique data.
What about developing cortical organoids with inner ear sensory-like structures?
This all fits with a larger trend of making more complicated organoids that include blood vessels and more. Furthermore, it goes along with the new papers reporting human embryo models made from stem cells in the lab.
Some important bigger-picture questions remain such as how long human embryo models can be ethically grown in the lab.
Should there be any kind of limits on the growth, size, or culture time for human brain organoids that exhibit increasingly complex features and possibly more interesting neural activities?
As to the human embryo models that are starting to be so similar to actual human embryos, I think limits make sense. For human brain organoids not so much. These structures are fairly far removed from actual human brains and reports of neural activity in them don’t show anything like coherent function on a consistent basis.