Replacing half a mouse’s brain with human glial cells, the cells that support neurons with a protective substance called myelin, doesn’t mean the mice are any more human, per se. Rather, researchers hope the advance will build on prior work that lets them understand more about diseases of the brain. Though cell cultures offer a certain degree of insight, the chance to see disease play out in more sophisticated models still reigns supreme.
Goldman and his team of colleagues initially incorporated 300,000 premature glial cells from donated human fetuses into the brains of ordinary lab mice. Within a year, the inaugural batch had multiplied to some 12 million cells, totally replacing the mice’s former cells. The replacement yielded massive changes to the animals’ cognitive output. With 100 times as many tendrils between synapses — the bridges between neurons — as the control mice, the humanized mice froze four times longer in response to a conditioned sound. Greater cognition made for stronger memory.
Human astrocytes, for example, a type of glial cell, are 10 to 20 times larger than mouse glial cells. They can communicate signals far more quickly, Goldman says. “It’s like ramping up the power of your computer.”
The Pinky and Brain scenario will not happen. The mice only do quite a bit better on the maze and other mouse tests
This could be useful for treating diseases in which the myelin sheath is damaged, such as multiple sclerosis, says Goldman, and he has already applied for permission to treat MS patients with the glial progenitor cells, and hopes to start a trial in 12 to 15 months.
Planet of Apes scenario is a no-go for now
They are moving the experiments toward more advanced models. He has set his sights on rats, though he doubts they’ll move much further. Monkeys and chimpanzees are probably a no-go, as toying with higher-order functions begins to introduce ethical concerns.
Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative proportion of mouse GPCs fell as a function of time, concomitant with the mitotic expansion and spread of donor hGPCs. By a year after neonatal xenograft, the forebrain GPC populations of implanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo.
SOURCES- Medical Daily, Journal of Neuroscience, New Scientist