Stem cells can differentiate into neurons, but can they integrate into the wider neural network and contribute to the function of the central nervous system? The evidence for this is scant. Even though transplanted stem cells can increase the function of the nervous system or decrease or halt the deterioration of the nervous system, there is little direct evidence that neurons made from stem cells can connect and signal to other neurons.
The laboratory of clinical neurologist Stuart Lipton at the Sanford-Burnham Medical Research Institute has used embryonic stem cells for this experiment. They differentiated these stem cells into neurons and implanted them into the brains of laboratory rodents. However, transplanting them, they also genetically engineered these neurons so that they would express genes from bacteria that encode fast-acting light-activated ion channels. These ion channels would cause the neurons to activate a nerve impulse if a light was shined on them. This provided a way to artificially activate these neurons to determine if they were connected to other neurons and integrated into the central nervous system and it neural network.
This technique is called “optogenetics,” and it is a relatively new field of molecular biology. By using genes from particular species of bacteria that encode light-activated ion channels, cells that normally do not respond to light can be engineered to respond to particular frequencies of light. The use of optogenetics in stem cells is also novel, but this increasingly powerful technology is capturing the imaginations of more and more scientists every day.
To continue with our story, what happened to the implanted stem cell-derived neurons when they were illuminated? They made nerve impulses, but ion changes were detected in neurons that were located far from the implanted neurons. The only reasonable explanation for these observations is that the implanted neurons are forming proper neural connections with other neurons and any nerve impulses established in the implanted neurons stimulate nerve impulses in connected neurons that then activate neurons in all the neural pathways connected to them.
Lipton said of his work, “We showed for the first time that embryonic stem cells that we’ve programmed to become neurons can integrate into existing brain circuits and fire patterns of electrical activity that are critical for consciousness and neural network activity.”
Even more interestingly, Lipton and his team implanted neurons into a portion of the brain known as the “hippocampus.” This structure helps to consolidate information from short-term memory to long-term memory. It also helps with spatial navigation. Since the rate at which neurons generate or “fire” nerve impulses varies from one region of the brain to another, Lipton wanted to know if his stem cell-derived neurons would fire at the same rate as those native neurons in the hippocampus of the laboratory rodent. The answer was a clear yes. The implanted neurons fired at roughly the same rate as the surrounding, endogenous hippocampal neurons. This suggests that the implanted neurons adapt and ultimately become physiologically like those neurons around them.
Lipton sees great potential for clinical treatments in this work: “Based on these results, we might be able to restore brain activity – and thus restore motor and cognitive function – by transplanting easily manipulated neuronal cells derived from embryonic stem cells.”
Lipton’s optimism is infectious to one extent, but I think we must temper it by realizing that Lipton shined lights on his neurons, and that this is something that we cannot do to the brains of human beings. However, if neurons that respond to other neurons can be made and implanted into the brains of Alzheimer’s disease patients, for example, then this could definitely restore cognitive ability in patients with neurodegenerative diseases.