In a recent study published in Cell Stem Cell, researchers have successfully transplanted human brain organoids into the brains of adult rats. The brain organoids not only survived in the rat’s brain, but they also integrated with the host brain both anatomically and functionally, offering evidence for their potential use in repairing damage in the brain.
What are brain organoids?
Brain organoids are structures generated from human pluripotent stem cells that closely resemble brain tissue, with a similar diversity of brain cell types and architecture to brain tissue. The brain has a limited repair capacity and so brain organoids have been developed as a potential way to treat traumatic brain injury, stroke, neurodegeneration, or other types of damage to the cortex. As Isaac Chen, one of the senior authors of the study puts it, “Brain organoids have architecture; they have a structure that resembles the brain.”
Previous research has shown that individual human neurons can be successfully transplanted into rodent brains. A more recent study that was published in Nature last year demonstrated that brain organoids can be successfully transplanted in the brains of newborn rats – and that the organoids could grow, mature and integrate into the rats’ brain circuits. These results suggest that brain organoids may hold promise as a treatment for cortical repair, and as a translatable and ethical alternative to foetal cortex transplantation for restoring brain function.
In this study, researchers investigated the integration of human cortical organoids with the adult rat visual cortex after transplantation (Figure 1). The brain organoids were cultivated in the lab for around 80 days and then grafted into the brains of adult rats that had injuries to their visual cortex. Within only 3 months, the transplanted brain organoids had assimilated with their host’s brain to a surprising degree – they became vascularised, had neuronal projections, and were forming synapses with the host’s neurons. Isaac Chen said, “We were not expecting to see this degree of functional integration so early. There have been other studies looking at transplantation of individual cells that show that even 9 or 10 months after you transplant human neurons into a rodent, they’re still not completely mature.”
The researchers used histological analysis and virus-based trans-synaptic tracing to characterize the quantity and distribution of the neuronal projections, and evaluated the spontaneous activity of organoid grafts using high-density multi-electrode probes. They showed a polysynaptic pathway between the retina of the host animals and organoid grafts, and that some neurons within the organoids responded to visual stimulation. Not only did the results show evidence of connectivity with the host brain in a visual network-specific manner, but also that the organoids survived robustly in the host’s brain.
A new hope?
The study has significant implications for future therapies aimed at repairing the brain after traumatic injuries, strokes, and other damages to the cortex. The current limited capacity for repairing the brain has led to a high burden of long-term neurological disabilities. Brain organoids derived from human pluripotent stem cells hold the promise of a potentially translatable alternative to foetal cortical grafts.
The study shows that brain organoids can integrate with the host brain both anatomically and functionally, and provides evidence for their potential use in repairing damage in the brain. However, the findings also highlight the need for further research to improve the structure of brain organoids and their integration with the host brain networks. Moreover, more research is needed to assess the long-term outcomes, and to further investigate the feasibility in humans. We are still a long way from using brain organoids in the clinic, but this study demonstrates the potential of using stem brain organoids to repair damage to the brain.