WIKIMEDIA COMMONS, NICOLAS P. ROUGIER
Neurons made from human embryonic stem cells (hESCs) can both send and receive nerve impulses when transplanted into the mouse brain, according to a report published today (November 21) in Proceedings of the National Academy of Sciences. The discovery provides some of the strongest evidence that hESC-derived neurons, which could be used to treat a variety of neurological disorders such as epilepsy, stroke, and Parkinson’s disease, can fully integrate and behave like regular neurons when transplanted into the brain.
“We’ve known for decades that [transplanted neurons] can receive information,” said Jason Weick of the University of Wisconsin, who was the lead author on the study. Once the cells are in the brain, he explained, their electrical activity can be simply recorded. The missing part of the puzzle was, he said, “Can the cells output to the brain?”
To find out, “they used some very...
Those clever tricks employed the powerful techniques of optogenetics. Specifically, the researchers expressed light-sensitive ion channels from algae in hESC-derived neurons such that they incorporated into the membrane. In response to light, these channels sent a flood of ions surging into the cell triggering it to fire an action potential. (Watch a video on optogenetics.)
When the engineered neurons were co-cultured with mouse neurons or transplanted into mouse brains that were later prepared as slices, the team could simply flip on a light—an LED linked to a fiber optic cable placed a few millimeters from the cells—and look for activity from the mouse neurons. Sure enough, the mouse cells were receiving impulses from the hESC-derived neurons, and conversely, the human cells could also receive impulses from the mouse neurons.
“[It is] the most convincing demonstration thus far of functional integration of human embryonic stem cell-derived neurons into existing neural networks,” said Steve Goldman of the University of Rochester Medical Center, who was not involved in the study. Indeed, echoed Song, “For the first time they were able to show that the cells can modulate the existing neurocircuitry.”
Researchers have shown previously that hESC-derived neurons transplanted into rat brains could modulate the animals’ behavior. Although this suggested functional integration, Song pointed out, “behavior doesn’t have enough resolution to tell you what exactly is happening.” The new study provides more definitive proof.
That said, Goldman thinks that showing how these cells function in a living animal will be an important next step. “Slice preparations are not the same as looking at the live brain,” he said.
Assuming the results hold true in live animals, the optogenetic approach could be used to accurately examine how the cells find their home and their partners, said Song. Furthermore, rather than simply being a tool for research, light-responsive neurons could be used to treat patients.
“We’re moving into the realm of treating animal models, at least, with cell replacement,” said Weick, “and at the same time being able to control the output of the transplant.”
Longer term, Weick envisages the same paradigm applying to humans. “Let’s say you are having a particularly bad day, your Parkinson’s symptoms are awful, but you’ve received this transplant [of cells] and you have an implantable light stimulation device,” he said. In that case, “you can simply ratchet-up the stimulation.”
J.P. Weick et al., “Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network,” Proceedings of the National Academy of Sciences, www.pnas.org/cgi/doi/10.1073/pnas.1108487108, 2011.