Reprogramming cell in adult central nervous system promotes regeneration of motor function axons after spinal cord injury

When a person experiences a spinal cord injury, the damaged neurons don’t regenerate, and this can lead to permanent physical and neurological pain. Researchers at Indiana University School of Medicine are studying how reprogramming a type of glial cell found along the spinal cord can promote regeneration of nerve fibers critical to motor function. 

Led by Wei Wu, PhD, assistant professor of neurological surgery and a primary member of Stark Neurosciences Research Institute, the researchers discovered a connection between the reprogramming of NG2 glial cells and robust axonal regeneration after spinal cord injury.  

“We unexpectedly uncovered a novel biological function of NG2 glia reprogramming in vivo, alongside with the generation of new neurons,” Wu said. “This reprogramming process may contribute to the reconstruction of residential neural networks essential for behavioral recovery.” 

Spinal cord injuries affect hundreds of thousands of people in the United States — with thousands more diagnosed each year — and there are no effective treatments. 

The research team, which published their findings in iScience, previously reprogrammed NG2 glia into new neurons in a spinal cord injury animal model. They did this using elevated levels of SOX2 — a transcription factor found inside the cell that’s essential for neurogenesis. 

When the spinal cord is injured, NG2 glia is one of three types of glial cells — supporting cells in the central nervous system — that respond to the injury site to form glial scar tissue. When modified, the cell reduces scaring and leads to overall improved function. 

Wu and his fellow researchers focused their investigation on the corticospinal tract — an essential pathway for movement — and serotonergic neurons, which play an important role in modulating the activity of spinal networks in motor functions. The axons for both pathways transmit commands from the brain to the spinal cord to control movement. 

Despite the pivotal roles of these two pathways in the central nervous system, they don’t regenerate on their own after injury, Wu said. Reprogramming NG2 in the spinal cord of the animal model not only promoted axonal regeneration across and beyond the lesion of the injury, but it also triggered the generation of new neurons, including those associated with the corticospinal tract and serotonin. 

“The in vivo experiments enable us to directly address the efficacy of the in vivo cell fate reprogramming as a strategy to produce new neurons in the adult mouse spinal cord,” Wu said. “By observing the effects within the spinal cord tissue, we can better understand how reprogramming promotes the neural circuit repair.” 

Wu said future studies are needed to better understand the reprogramming-induced regeneration process and develop glia reprograming as a therapeutic strategy. 

“Both the regenerated axons and new neurons are likely playing crucial roles in promoting the neural repair after spinal cord injury,” Wu said. “By translating our preclinical findings into clinically viable therapies, we hope to provide effective treatments that enable individuals with spinal cord injuries to regain lost function and enhance their independence and mobility.”