While neurons normally fail to regenerate after spinal cord injuries, neurons formed from human induced pluripotent stem cells (iPSCs) that were grafted into rats with such injuries displayed remarkable growth throughout the length of the animals' central nervous system. What's more, the iPSCs were derived from skin cells taken from an 86-year-old man. The results, described in the Cell Press journal Neuron, could open up new possibilities in stimulating neuron growth in humans with spinal cord injuries
"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 and that these capabilities persist even in neurons reprogrammed from very aged human cells," said senior author Mark Tuszynski, MD, PhD, professor of neurosciences and director of the UC San Diego Center for Neural Repair.
After Dr. Tuszynski and his colleagues converted the skin cells into iPSCs, which can be coaxed to develop into nearly any other cell type, the team reprogrammed the cells to become neurons, embedded them in a matrix containing growth factors, and then grafted them into 2-week-old spinal cord injuries in rats.
Three months later, the team found mature neurons and extensive nerve fiber growth across long distances in the rats' spinal cords, including through the wound tissue and even extending into the brain. Despite numerous connections between the implanted neurons and existing rat neurons, functional recovery of the animals' limbs was not restored. The investigators noted that several iPSC grafts contained scars that may have blocked beneficial effects.
Dr. Tuszynski, along with lead author Paul Lu, PhD, of the UC San Diego Department of Neurosciences, and their collaborators are now working to identify the best way to translate neural stem cell therapies for patients with spinal cord injuries, using grafts derived from the patients' own cells.
Neuron, Lu et al.: "Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells After Spinal Cord Injury."