Transplanting human cells into animal brains brings insights into development and disease along with new ethical questions.
Credit: Raquel Real, Manuel Peter, Rick Livesey and Vincenzo De Paola
“We expected some connectivity, but we were quite stunned at how specific the responses were,” says Bonin. “There are a million ways this could have failed.” De Paola’s team did the same transplant experiment using neurons made from cells from people with Down’s syndrome. They found that these neurons formed less dynamic networks, with lower neural activity — but it’s unclear what relationship, if any, exists between the two features. The team is exploring that next. “We can do that experiment in this model. Obviously, we cannot do it in a human adult or fetal brain,” De Paola says.
To overcome these limitations, neuroscientists have begun to transplant organoids into an animal’s brain to more closely model the complexity of human brain circuits and how they go awry in disease. Gage’s group now plans to transplant brain organoids made from the cells of people with Alzheimer’s disease into healthy mouse brains and, conversely, healthy human organoids into mouse brains that mimic Alzheimer’s symptoms. The aim is to tease apart which cell types — the neurons themselves, or other brain cells such as astrocytes — contribute to the inflammation seen in the disease.“For the first time, we are able to monitor living human brain tissue in a disease context,” Gage says.
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