A brain tissue transplant could become a future therapy for the treatment of vision loss. A study published in the journal Cell Stem Cell, a team of US researchers show that groups of lab-grown neurons, brain organoids, can integrate with rat brains and respond to visual stimulation such as flashing lights.
Decades of research have shown that it is possible to transplant human and rodent neurons into rodent brains, and more recently, human brain organoids have been shown to be able to integrate with developing rodent brains.
However, it has not yet been explored whether these grafts of organoides they can be functionally integrated with the visual system of injured adult brains.
“We focused not just on transplanting individual cells, but on transplanting tissue,” says lead author H. Isaac Chen, professor of neurosurgery at the University of Pennsylvania. “Brain organoids have architecture; They have a structure that resembles the brain. We were able to look at individual neurons within this structure to gain a deeper understanding of the integration of the transplanted organoids.”
The researchers cultured human stem cell-derived neurons in the laboratory for about 80 days before grafting them into the brains of adult rats that had suffered damage to the visual cortex.
Within three months, the grafted organoids had integrated with their host’s brain: they created blood vessels, grew in size and number, sent out neural projections, and formed synapses with the host’s neurons.
The team used fluorescently tagged viruses that hop across synapses, from neuron to neuron, to detect and trace physical connections between the organoid and the host rat’s brain cells. «By injecting one of these viral markers into the animal’s eye, we were able to trace the neural connections downstream of the retina.Chen points out. The tracker reached the organoid.
Within three months, the grafted organoids had integrated with their host’s brain.
Next, the researchers used electrode probes to measure the activity of individual neurons within the organoid when the animals were exposed to flashing lights and alternating black and white bars. “We saw that a good number of neurons within the organoid responded to specific orientations of light, which was not
It gives us evidence that these organoid neurons were not only able to integrate with the visual system, but were also able to take on very specific functions of the visual cortex.”
The team was surprised by the degree to which the organoids were able to integrate in just three months. «We didn’t expect to see this degree of functional integration so soon.says Chen.
Neural tissues have the potential to rebuild damaged areas of the brain, Chen says. «We haven’t figured everything out, but this is a very solid first step.. Now, we want to understand how organoids might be used in other areas of the cortex, not just the visual cortex, and we want to understand the rules that guide how organoid neurons integrate with the brain so that we can better control that process and make it happen. faster”.