Scientists from the University of Rochester say they have made mice significantly smarter by injecting them at a young age with human brain cells, according to a study published in the journal Cell Stem Cell.
The researchers used immature glial cells removed from human fetuses that had been donated for research. Glial cells are a type of nerve cell that do not transmit signals (as neurons do) but provide a wide variety of other important functions for the nervous system, including forming the myelin sheath around nerve cells and supporting the neurons.
Once injected, the human cells began to destroy native mouse glial cells and began to take over the animal’s brain.
Mouse cells wiped out
“We could see the human cells taking over the whole space,” researcher Steve Goldman said. “It seemed like the mouse counterparts were fleeing to the margins.”
The immature glial cells took the form of mature glial cells known as astrocytes, due to their star-like shape. Astrocytes are known to help strengthen the connections (synapses) between neurons and help coordinate electrical communication across synapses.
Within a year’s time, the 300,000 injected human cells had multiplied to 12 million astrocytes and had completely replaced all mouse astrocytes. The mouse neurons, however, seemed unaffected by this process.
Because human astrocytes are 10 to 20 times bigger than mouse astrocytes and have 100 times more tendrils, they can coordinate many more neuronal signals at a much higher speed. Therefore, the researchers hypothesized that mice with human astrocytes would be smarter than other mice.
A series of standard cognition and memory tests seemed to confirm this hypothesis. The mice with hybrid human brains learned significantly faster, navigated mazes better and had better memories than a control group with non-modified brains.
“These were whopping effects,” Goldman said. “We can say they were statistically and significantly smarter than control mice.”
Creating a life form that combines human and animal traits raises a series of ethical questions, of course. The researchers made several attempts to allay such concerns. They noted that the purpose of their research is not to create smarter mice, but to create a better model of the human brain to enable medical research into human diseases.
Goldman has already performed one such study on mice with a hampered ability to produce myelin, which insulates neurons. Destruction of myelin is associated with diseases such as multiple sclerosis (MS).
In these mice, the human glial cells took the shape not of astrocytes, but of oligodendrocytes, which specialize in producing myelin. Goldman has already applied for permission to test such a therapy on human MS patients.
The researchers also sought to downplay concerns that the brains of the modified mice were in any way human.
“It’s still a mouse brain, not a human brain,” Goldman said. “But all the non-neuronal cells are human.”
The degree to which the mouse brains have become human is unclear, however.
“It would be interesting to find out whether the human astrocytes function the same way in the mice as they do in humans,” said stem cell researcher Fred Gage, of the Salk Institute in La Jolla, California. “It would show whether the host modifies the fate of cells, or whether the cells retain the same features in mice as they do in humans,” he said.
Yet Goldman acknowledged the validity of such concerns, noting that the researchers themselves had decided against injecting human cells into monkeys for just such reasons.
“We briefly considered it but decided not to because of all the potential ethical issues,” Goldman said.
“If you make animals more human-like, where do you stop?” asked Wolfgang Enard of Ludwig-Maximilians University of Munich in Germany, who has engaged in similar research.