New Method to Create Human Neural Stem Cells May Regenerate Spine in Rats



Photo Credit: Mark Ellisman and Thomas Deerinck UC San Diego

Scientists at the University of California San Diego School of Medicine have created spinal cord neural stem cells (NSC) from human pluripotent stem cells (hPSCs), which could feasibly represent a source of transplantable cells for repairing spinal cord injuries.

The research, which was published in the journal Nature Methods, showed that the human spinal cord NSCs can be maintained over long periods in culture and, when transplanted into the injured spinal cords of rats, transformed into all the major neural cell types, the neurons or nerve cells responsible for sending signals in the brain and spinal cord, and the glia, which play a key supporting role to neurons. The grafts were particularly effective in creating axons, which carry signals from one neuron to another,  and promoting regeneration of the corticospinal tract, which controls our ability to move our arms and legs.

“In grafts, these cells could be found throughout the spinal cord, dorsal to ventral. They promoted regeneration after spinal cord injury in adult rats, including corticospinal axons, which are extremely important in human voluntary motor function. In rats, they supported functional recovery.”- Hiromi Kumamaru, M.D., Ph.D.

Cell-based therapies typically require a large number of specialized cells, which requires a series of steps changing embryonic stem cells into the desired cell . The UCSD team developed a faster process, generating large numbers of NSCs in the lab.

The researchers say spinal cord NSCs have the potential to be used for repairing spinal cord damage but to date, no one has managed to generate them in the vitro. Moreover, the ability to use such cells for spinal cord repair would only be feasible if they can generate all of the key cell types required inside the body, including the different types of neurons and supporting glial cells.

Initial experiments transplanting the cells into rats with spinal cord injuries showed that the grafted stem cell-derived human spinal cord NSCs survived and readily extended axons into the injured host spinal cord, even months after transplantation. Within three months 80% of the graft-derived cells expressed neuronal markers, and by six months post-transplantation, the populations of graft-derived cells expressed markers for other key support cells in the brain (called  oligodendrocytes and astrocytes) and neurons.

“These results indicate that H9-hESC-derived spinal cord NSCs can generate the three cardinal neural lineages in vivo (in the body),” the team wrote. More detailed analyses suggested that by six months post-transplantation, the spinal cord NSC grafts had transformed into a variety of neuronal subtypes that were helping to promote 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 other neural disorders such as ALS.

The researchers say their approach offers the potential for generating the large numbers of cells needed to treat spinal cord injury in a clinical setting, although they acknowledge that further studies will be needed to test the safety and effectiveness of the approach before testing it in people.


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