During the past decade, researchers have learned to turn human pluripotent cells into neurons. They have tested these neurons in cell cultures, where they seem to function like normal neurons. They have implanted these human neurons in mouse brains, where human cells thrive like normal cells. The big question is whether they do the work of brain cells. Long before cells are implanted in human brains, researchers want to know whether the cells will function properly in any working brain, starting with a mouse brain.
Now comes evidence that the implanted cells seem to be fully function, integrated in the basic process of the mouse brain. In the report published in the November 21 issue of PNAS, researchers at the University of Wisconsin report on their use of a new technology, optogenetics, to test the function of the implanted cells. This technology uses light rather than electricity to stimulate implanted neurons. The result, it is claimed, is the best evidence so far that implanted cells are integrated fully into the functioning brain, sending and receiving signals as part of living neural networks.
”We show for the first time that these transplanted cells can both listen and talk to surrounding neurons of the adult brain,” said lead author Jason P. Weick in a press release from the University.
By using optogenetics, this study provides evidence that implanted human neurons derived from pluripotent stem cells can become functionally integrated into systems of a living brain, sending and receiving signals from surrounding or “host” cells and interacting with brain circuitry in a way that is consistent with normal brain rhythms.
According to the paper published in PNAS, the neurons derived from pluripotent cells “can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing…”
What’s more, the researchers discovered that optogenetics may someday have a clinical use far beyond its value as a research tool. The fact that implanted cells can be stimulated using a light signal may someday become part of the way stem cells are used on human patients. According to Su-Chun Zhang, also an author of the report, “You can imagine that if the transplanted cells don't behave as they should, you could use this system to modulate them using light.”
Still more challenges must be met before neurons derived from human pluripotent cells are implanted successfully in the human brain. But this study advances the field in a critically important way and provides strong evidence that implanted cells might one day take on the function of damaged cells in the living human brain.
If human brains can be regenerated even in highly limited ways, the consequences will be profound. The most obvious applications will be to treat patients who have lost some part of brain function due to stroke, brain injury, or disease.
And if that becomes possible, it is not hard to imagine that the same technology will be used to regenerate the brains of those whose only “disease” is aging. Furthermore, it is quite likely that at some point in the future, implanted neurons derived from pluripotent cells will be genetically modified first, perhaps to prevent disease but also perhaps to enhance the performance of the brain into which they become functionally integrated.
It is important to stress that treatment for complex disorders of the brain, such as Alzheimer’s Disease, are still a long way off. But this research is an important step, showing that the basic concept of stem cell treatment may provide one form of treatment. But is that becomes possible, it may also become possible to enhance the cognitive capacity of people without disease.
The milestone reported here is just one more step--of which there must be hundreds or thousands--leading us closer to the day when human brains might be regenerated or renewed. Few will object to the use of such treatments to restore functioning neurons to those with Huntington's disease or early onset Alzheimers. And if early onset Alzheimers, why not late onset? And if late onset dementia, why not age-related cognitive decline? At what point do we cross the line from therapy to enhancement, and does such a line even exist?
So while we stress that these treatments are not available today--and may never be--they will very likely come in time. And when they come, they will open the path for completely new ways to extend the functional lifespan of the human brain.
The report, entitled "Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network," appeared in the Nov 21, 2011 issue of PNAS.