Neurons grafted into rats with spinal cord injuries have sprouted tens of thousands of axons that extend the entire length of the rodents’ central nervous system.
The neurons used here were derived from a type of human stem cell called induced pluripotent stem cells (iPSCs), which have the ability to become almost any kind of cell in the body. “These findings indicate that intrinsic neuronal mechanisms readily overcome the barriers created by a spinal cord injury to extend many axons over very long distances,” says Mark Tuszynski from the University of California, San Diego, in a news release.
Tuszynski, Paul Lu, and a UC San Diego team converted skin cells that were taken from a healthy 86-year-old man into iPSCs, which were then genetically reprogrammed to become neurons. After the neurons were embedded in a matrix containing growth factors, they were grafted into the site of two-week-old spinal cord injuries in rats.
Three months later, the human iPSC-derived axons had extended long distances: through the white matter of the injury site, even penetrating gray matter to form synapses with the rat’s neurons. Similarly, axons extending from the rat’s neurons pierced the iPSC grafts to form their own synapses.
But despite how numerous connections formed between the implanted human cells and the rats’ own cells, the researchers didn’t detect functional recovery of the rodents’ use of their affected limbs. The human axons were not myelinated -- the white insulating sheath didn’t form around the nerve fibers the way they would with the rodent axons. The researchers suspect that scars contained in the iPSC grafts may have blocked the beneficial effects of the new axons.
Moving the technique to human therapy too quickly would be a bad idea. “The enormous outgrowth of axons to many regions of the spinal cord and even deeply into the brain raises questions of possible harmful side effects if axons are mistargeted,” Tuszynski explains. “We also need to learn if the new connections formed by axons are stable over time, and if implanted human neural stem cells are maturing on a human time frame -- months to years -- or more rapidly.”
He likens it to nuclear fusion: If contained, you get energy, but if it’s not contained, you get an explosion. "Too much axon growth into the wrong places would be a bad thing," he tells U.S. News and World Report. The team is now testing iPSCs, embryonic stem cell-derived cells, and other stem cell types for repairing spinal cord injuries.
The work was published in Neuron this week.
