A group of scientists led by Jonas Frisen at the Karolinska Institute in Stockholm, Sweden, have identified cells in the spinal cord that normally seem to form scar tissue after an injury but may, in fact, be able to form the kind of cells that restore spinal cord function. If the cells' differentiation can be manipulated, they could eventually lead to new, non-surgical therapies for spinal cord injuries, which affect more than 30,000 people a year.

Reporting this month in PLoS Biology, the group used transgenic mice to map the fate of cells in the central canal of the spinal cord, where neural stem cells had long been suspected to reside but had not been definitively identified. These experiments indicated that a fairly specialized cell type expressing both Nestin and FoxJ1 slowly proliferated and displayed some stem cell characteristics. These cells turned out to be the ependymal cells that line the central canal of the spinal cord; they are covered with cilia and help cerebrospinal fluid circulate around the central nervous system. Frisen and his team discovered that ependymal cells can readily be expanded in culture to generate clusters of neural stem cells known as neurospheres. The neurospheres could be differentiated into neurons, astrocytes and oligodendrocytes in vitro and were able to self-renew in vivo, implying that spinal cord stem cells are largely contained within the ependymal cell population.

The ependymal cells became particularly interesting because they respond to spinal injury. The group injured the mice by making a small cut in an area of the spinal cord. The ependymal cells began to migrate toward the injury, and they lost their characteristic shapes and contributed heavily to scar tissue. Scar tissue can prevent further damage to the area, but it also prevents healing by filling the injury site with non-functioning tissue. One goal of regenerative medicine is to redirect cells from forming scar tissue to becoming working tissue.

Usually the growing scar tissue actually sends out chemical signals that inhibit the growth of new support cells, preventing the complete recovery of the spinal cord. Excitingly, however, in vivo experiments showed that ependymal-derived cells do not send out these signals. The majority of ependymal-derived cells in the scar resembled astrocytes, expressing Vimentin and Sox9 proteins, but most of them did not express glial fibrillary acidic protein, which is a classic marker of this cell type. This means that the glial scar is comprised of two separate populations of astrocytes — those that are ependymal-derived and those that are mainly reactive, resident astrocytes. In fact, a small proportion of ependymal-derived cells displayed the protective and healing properties of oligodendrocytes, producing the protective myelin sheath that surrounds axons. The team discovered that over ten months, a small number of ependymal-derived oligodendrocytes appeared outside the scar and were associated with a protein indicating that they contribute to axonal re-myelination and recovery of central nervous system function.

“This is a very nice piece of biology, and the idea that it might eventually lead to a non-surgical therapy for spinal cord injuries is valid,“ says Jack Price, professor of developmental neurobiology at Kings College London, but he feels that more evidence is required to conclusively show that ependymal cells are a useful source of oligodendrocytes. Pantelis Tsoulfas, associate professor at The Miami Project to Cure Paralysis in Miami, Florida, agrees. The research helps scientists understand the repair process after spinal cord injury, but, he says, “I am not sure how clear the path is to clinical solutions.” However, he believes the techniques will be useful to track cells after grafting neural precursors or any other interventions to repair the injury.

Moving forward, Konstantinos Meletis, first author on the paper, is keen to genetically trace other cell populations in the adult spinal cord, such as oligodendrocyte progenitors or subpopulations of ependymal cells, as well as to ablate the differentiated progeny to learn the importance of the ependymal reaction to injury. Once researchers know which cells in the spinal cord can behave like stem cells, Meletis hopes they can find drugs that can help the spinal cord repair itself after an injury.