This is a histology of a rat brain implanted with human brain organoids. Credit: Jgamadze et al.
In a study published in the journal cell stem cell On February 2, researchers showed that brain organoids (clusters of neurons grown in the lab) can integrate with rat brains and respond to visual stimuli such as flashing lights.
Decades of research have shown that individual human and rodent neurons can be transplanted into rodent brains, and recently demonstrated that human brain organoids can integrate with the developing rodent brain. It has been. However, whether these organoid grafts can functionally integrate with the visual system of the injured adult brain remains to be investigated.
“We focused on actually transplanting tissues, not just transplanting individual cells,” says senior author H. Isaac Cheng, a physician and assistant professor of neurosurgery at the University of Pennsylvania. says. “Cerebral organoids have structures. ”
The researchers cultured human stem cell-derived neurons for about 80 days in the lab before transplanting them into the brains of adult rats with damaged visual cortex. The transplanted organoid he integrated with the host’s brain within three months. It became vascularized, increased in size and number, and sent neuronal projections to form synapses with host neurons.
The team utilized fluorescently tagged viruses that hop along synapses from neuron to neuron to detect and track physical connections between host rat organoids and brain cells. “By injecting one of these viral tracers into the animal’s eye, we were able to follow neuronal connections downstream from the retina,” says Chen.
The researchers then used electrode probes to measure the activity of individual neurons within the organoids when the animals were exposed to flashing lights and alternating white and black bars. “We found that a significant number of neurons within the organoids responded to light in specific directions. It shows that it’s done. Cortex.”
The team was amazed that the organoids could be integrated in just three months. “We didn’t expect to see this degree of feature integration so early,” he says. “Other studies looking at transplantation of individual cells have shown that 9-10 months after transplanting human neurons into rodents, they are still not fully mature. increase.”
“Neural tissue has the potential to remodel damaged brain regions,” Chen says. “We haven’t solved everything, but this is a very solid first step. Now we want to understand how organoids can be used in other areas of the cortex, not just the visual cortex. We also want to understand the rules that guide how organoid neurons integrate with the brain, and that happens faster.
See also: “Structural and functional integration of human forebrain organoids with the visual system of injured adult rats”, Denise Jamadze, James T. Lim, Zijiang Chan, Paul M. Harary, James Jami, Covina Mensah Brown, Christopher D. Adam, Ethan Mirza Hariri, Shika Singh, Jiahe Ben Gu, Rachel Blue, Mehek Dedia, Marissa Hu, Fadi Jacob, Shuyu Chen, Kimberly Gagnon, Matthew Sergesson, Oceane Hurshet, Imon Rahman, Huadong Wang, Fu Huchang, Rui Xiao, Diego Contreras, John A. Wolf, Hongjun Song, Guo-li Ming,
Han-Chiao Isaac Chen, February 2, 2023, cell stem cell.
DOI: 10.1016/j.stem.2023.01.004
This research was supported by the Department of Veterans Affairs, the National Institutes of Health, and Dr. Miriam and the Sheldon G. Adelson Foundation for Medical Research.
