These tiny little blobs Each speck of brain tissue was just a few micrometers wide, and they were lab-grown. Stanford University scientists created them using stem cells from human beings to grow three-dimensional clusters of tissue. These simplified brain organoids are called brain organoids and provide insight into neurological and developmental conditions.
But they’re not nearly as complex as the real thing, so to boost their realism, researchers elsewhere have tried transplanting human organoids into the brains of rodents. In past experiments, those cells failed to integrate into the animals’ brains. This time, it worked: The organoids formed connections with the animals’ own brain circuits, a sign that these bundles of cells can develop more sophisticated features.
The Stanford team transplanted these clusters of human cells into the somatosensory cortices of newborn rats—the area that processes sensory information, such as touch, from across the body. These organoids eventually occupied about one-third the brains in the rat over the course of several months. Today, the research was published in The Journal Nature. “This definitely pushes forward what organoids can do in terms of their functional integration into the brain,” says H. Isaac Chen, assistant professor of neurosurgery at the University of Pennsylvania, who wasn’t involved in the study.
Chen and others had previously tried similar experiments in adult rodents, but those transplanted organoids didn’t successfully mature. In the latest attempt, the Stanford scientists transplanted the organoids early in development, when the young rats’ neuronal circuits weren’t fully formed. The adult brain is much less plastic, meaning it’s not able to change and form new connections as easily. “The nervous system has a way of shutting down development,” said Sergiu Pasca, professor of psychiatry and behavioral sciences at Stanford and the corresponding author on the study, in a press briefing ahead of the paper’s publication. “We went in and we transplanted before the ability for cells to form connections had stopped.”
Pasca and his collaborators found, in a break with previous research, that human nerve cells transplanted into rats grew nerve fibres. These fibers then formed synapses among rat neurons. These connections don’t exist in brain organoids grown in a dish, a major limitation that has driven scientists to transplant orgaonids into living animals.
“We know that the brain develops and works by receiving activity, either from endogenous networks or from the outside world through sensory stimulation of the tissue,” says Paola Arlotta, a professor of stem cell and regenerative biology at Harvard University, who wasn’t involved in the Stanford research. Sensory stimulation plays a vital role in normal brain development and the formation of neural pathways.
The organoids grew and incorporated with tissue. They also showed characteristics that were not possible in cells grown in a dish. Some of the organoids were grown by Stanford scientists from Timothy syndrome cells, which are cells from severe cases of autism. When transplanted into rats, the organoids developed abnormal dendrites—the treelike branches that extend from neurons and allow them to communicate with other cells. These defects hadn’t been seen in earlier organoid experiments without animals.