Potential Strategy of Repairing Spinal Cord Injury with Stem Cells

A spinal cord injury is damage to the spinal cord that results in a loss of function, such as mobility and/or feeling. Damage to the spinal cord can occur in a variety of ways, although the most common cause is due to external trauma. The spinal cord does not have to be severed for a loss of function to occur. Most people with spinal cord injury have their cord intact, but the damage to it results in loss of function.

Currently, there is no cure and scientists are working to make further advances in treating spinal cord injuries. A new study by researchers at the Karolinska Institutet in Sweden demonstrated that spinal cord injury may be repaired by stem cells. Using a mouse model, the researchers showed that it is possible to stimulate stem cells in the mouse spinal cord to form large amounts of new oligodendrocytes, cells that are necessary for neurons transmitting signals, which aid in repairing the spinal cord after injury.

Their findings, “A latent lineage potential in resident neural stem cells enables spinal cord repair,” were recently published in Science.

An oligodendrocyte is a type of neuroglia found in the central nervous system of invertebrates and vertebrates that functions to produce myelin, an insulating sheath on the axons of nerve fibers. Oligodendrocytes readily regenerate and replace myelin membranes around axons in the adult mammalian central nervous system (CNS) following injury.

“Injuries to the CNS are inefficiently repaired. Resident neural stem cells manifest a limited contribution to cell replacement. We have uncovered a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord,” the researchers wrote.

The researchers carefully characterized spinal cord stem cells at a genetic level in mice, and found that the stem cells’ DNA was receptive to signals that stimulate the formation of new oligodendrocytes. “We integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) to study lineage potential in adult ependymal cells of the mouse spinal cord. We found that the genetic program for oligodendrocyte generation is accessible in ependymal cells,” noted the researchers.

Enric Llorens-Bobadilla, a researcher at the department of cell and molecular biology at Karolinska Institutet, explained: “We found that the stem cells were not locked into forming scar tissue and understood how we could nudge them in another direction to also form cells that contribute to repair.”

By controlling which genes were activated in the stem cells, an abundant generation of new oligodendrocytes was stimulated, leading to improved nerve fiber function in the damaged spinal cord.

“Ectopic expression of the transcription factor OLIG2 unveiled abundant stem cell–derived oligodendrogenesis, which followed the natural progression of oligodendrocyte differentiation, contributed to axon remyelination, and stimulated functional recovery of axon conduction. Recruitment of resident stem cells may thus serve as an alternative to cell transplantation after CNS injury,” concluded the researchers.

Principal investigator Jonas Frisén, professor at the department of cell and molecular biology, Karolinska Institutet, noted that their findings showed that it is possible to affect stem cells in the nervous system so that they can contribute to functional recovery. “Although the studies were done in mice and are not directly translatable to humans, they indicate a conceptually new strategy for stimulating repair after damage to the nervous system.”

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