New Method to Create Human Neural Stem Cells Can Regenerate Spine in Rats, Study Shows

Human spinal cord neural stem cells (NSC), created using an innovative method, were seen to regenerate functional neurons in the damaged tissue of rats with spinal injuries, according to researchers.

Their study, “Generation and post-injury integration of human spinal cord neural stem cells,” was published in the journal Nature Methods.

Spinal cord NSC were already known to have great potential to regenerate damaged spinal cords and re-establish the neural circuitry. However, these cells had never been created in the lab (in vitro).

Now, a research team from the University of California, San Diego, used human pluripotent stem cells (hPSCs), an unspecialized cell type capable of giving rise to every cell type of the human body, to generate spinal cord neural stem cells.

“Scientists have been very enthusiastic about the potential to use neural stem cells to treat a number of spinal cord disorders, including spinal cord injury, amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy,” Rosemarie Hunziker, PhD, director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Tissue Regeneration Program, said in a press release.

“A real bottleneck in bringing this innovation to patients, however, is the ability to control the cell’s identity as a particular functional nerve cell, while preserving its ability to proliferate and provide a large number of these cells,” Hunziker said.

Cell-based therapies typically require a large number of specialized cells. To obtain such numbers, the first step often consists of the proliferation of the undifferentiated embryonic stem cells until the required cell numbers are reached. Later, cells are differentiated into the desired cell type in processes that usually inhibit proliferation.

A novel critical aspect of the protocol described by Mark H. Tuszynski, an MD and PhD, and professor of neurosciences at the Center for Neural Repair, University of California, San Diego, and his team’s ability to maintain the proliferative capacity of differentiating cells.

The team developed a cell culture system able to generate large numbers of NSC in vitro while maintaining their identity as neural progenitor cells. The cocktail of proteins added to the system promoted not only cell growth but also blocked factors in the cell that inhibit growth.

“Our concoction both drove cell growth and removed factors that block cell growth, resulting in a cell line of spinal cord neural stem cells that we were able to keep growing and expanding,” Tuszynski said.

Hiromi Kumamaru, MD, PhD, and first author of the study, also commented on the achievement.

“With the ability to expand and maintain large numbers of undifferentiated neural stem cells, we believe that advancement to human clinical trials could be in a time frame of as little as five years,” he said. “However, the safety and efficacy of these cells will first have to be established in additional studies in rats and non-human primates.”

Neural stem cells were then transplanted into a rat model of spine injury, demonstrating the cells’ ability to differentiate into more specialized types of spinal cord nerve cells, occupying multiple sites along the spine, a status that was maintained for prolonged time periods.

The differentiated neurons were found to have large numbers of nerve fibers over long distances, innervating their target tissues and promoting a robust spinal cord regeneration.

The team concluded that the ability of NSC to differentiate into multiple types of spinal cord neurons may be extremely valuable for testing potential therapies for numerous neural disorders such as ALS.

“Spinal cord NSC could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders,” researchers concluded.

This study was supported by grants from the NIBIB and the National Institute of Neurological Disorders and Stroke (NINDS).