Human brain organoids have been implanted into mice that are missing half their brain. Tiny versions of the human cerebral cortex – a region involved in memory, movement and thinking – were put into mice that lacked this major brain region. Not only did the organoids integrate into the mice’s brains, they also restored most of their cognition.
How better ways of screening drugs could soon lead to thousands fewer animal tests Sergiu Pașca at Stanford University in California and his colleagues genetically engineered mice to lack more than 90 per cent of their cortex, or about half their brain. These mice only experience some memory and movement deficits, since their brain adapts to compensate for their missing cortex, says Pașca. In about half of these mice, the team surgically implanted four human brain organoids, generated by bathing human stem cells in chemicals for about 40 days.
These filled the cavity in each of the mice’s skulls, producing what the researchers called XCX mice. The remaining mice, apallial mice, didn’t receive the transplants. A few months later, the apallial mice performed worse in a memory test, where they had to navigate a maze, than a third group of normal mice.
But this deficit was almost completely reversed in the XCX mice. The XCX mice also had a gait between that of the apallial and normal mice. Scans revealed that the organoids had grown to form cortex-like grafts.
This builds on prior studies that have implanted human brain organoids into rat or mouse brains, but without such a large part of the rodent brain being missing initially, says Pașca. These studies only showed that such organoids can alter cognition, rather than improving it, he says. For instance, in one study, light stimulated human brain organoids in rats to make them anticipate water.
The grafts in the latest study were also the first to contain a kind of nerve cell, called von Economo neurons, that influences social skills, as well as neurons that extended from the cortex to the spinal cord. The latter could explain why these grafts reduced impairments in motor skills, says Balmuș. The team’s organoids were larger and more akin to the human cerebral cortex than those used in previous experiments, says Pașca.
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