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article imageOp-Ed: Using human brain cells to smarten up the mouse

By E. Paul Zehr     Dec 3, 2014 in Science
The Journal of Neuroscience reports that brain cells from one animal species can be transplanted into that of another species and thrive. With an extent and relative rapidity, implanted human brain cells can actually take over the brains of mice.
Before going onward, let’s first go back to March of 2013. Xiaoning Han and colleagues in the laboratories of Steven Goldman and Maiken Nedergaard at the University of Rochester Medical Center published a paper that answered an interesting question—was it possible to enhance the neural processing ability of one species by surgically implanting and grafting cells from the brain of another “more advanced” species? In other words, can you make a brain smarter?
These scientists were interested in the extent of “biocompatability” in the mouse brain with certain evolutionary adaptations in human brain cells. The glial cells (called astrocytes because they are vaguely star-shaped) in human brains are much bigger and more complex than those of the mouse. Astrocytes, which don’t produce electric signals like all other neurons, are critical as physiological support and protection for the processing neurons. Although they don’t directly transmit information, glial cells are critically important in calcium signalling. This signalling is very important for overall brain activity and human astrocytes do it three times faster than mouse astrocytes.
What would happen if you grafted human glial progenitor cells—the stem cells in the brain that would normally become astrocytes—into the forebrain of immunosuppressed mice? Would the human cells survive in the mouse brain? Probably, given that cell implantations had been done previously. More importantly, would the human astrocytes offer any advantage to the mice with the implanted cells?
The answer to almost all questions was “yes”. Han and colleagues found that human glial cells thrived in the mouse forebrain, could propagate calcium signals at the rate usually found in the humans—that’s 3 times the rate normally found in mice—strengthened signal transmission between neurons (long-term potentiation underlying learning and memory formation) and affected behaviour.
Behaviors included fear conditioning, maze learning, and locating of new objects in the mouse environment. “Enhanced” chimeric mice with engrafted human glial cells had improved performance all around. In simple terms chimeric mice were made smarter by implantation of human brain cells. This study, of course, represented an important test that cross-species grafting techniques could be a useful way to modify and examine brain function.
Many issues need to be addressed before we get too excited about boosting intelligence with cellular implantation. An important scientific outcome the underlines functional brain evolution is that astrocytes have important roles in neural processing. A key limitation is the need for massive immunosuppression to ensure that the host animal continues to accept the donor tissue. Further studies could end up guiding the way we examine, understand and treat the brain and neurological disorders.
Another limitation of the 2013 study was that the long term viability in the mouse brain of those implanted human glial progenitor cells was unknown. How long would the cells survive and what would they do in beyond a few weeks and months? This is our segue back to the present.
The 2014 Journal of Neuroscience study of Martha Windrem and colleagues used an expansion of the protocol from 2013. Now, though, they studied the long term effects of engrafting human glial progenitor cells into the forebrains of neonatal mice. They were particularly interested in what would happen to the mouse glial progenitor cells in the mouse brain after engrafting with human cells. What they found was stunning.
The relative proportion of mouse glial progenitor cells steadily fell over time while that of the human cells increased in the mouse brain. The scientists found that after a year the population of glial progenitor cells found in the mouse forebrain were almost entirely of human origin. This means that the implanted human cells “outcompeted” and eventually replaced the host mouse cells.
There are two main takeaways from this study. The first is the exciting ability to alter the long term structure and function of a brain in one species by engrafting cells from another species. Just on its own this opens up many avenues for study of brain function that could have staggering therapeutic applications in neurological and neurodegenerative disorders. The second, though, is a bit more cautionary.
It’s not a given that we should have predicted that the implanted cells would so quickly and completely outcompete and “infect” the host brain. In fact, the scientists themselves wrote that they “were surprised to note that the forebrains of these animals were often composed primarily of human glia and their progenitors.” What other cellular interactions are disrupted by this effect on the astrocytes? What long term changes in brain structure and function may arise from this and what are the implications for behaviour?
We can anticipate with some excitement what the extension of this work may reveal. At the same time, this work and projects like it need to proceed with appropriate caution.
© E. Paul Zehr (2014)
E. Paul Zehr is professor and science communicator at the University of Victoria. His books “Becoming Batman”, “Inventing Iron Man”, and “Project Superhero” use superheroes as metaphors for popularizing science.
This opinion article was written by an independent writer. The opinions and views expressed herein are those of the author and are not necessarily intended to reflect those of
More about Stem cells, Astrocytes, Neurology, Neuroscience, plasticity
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