Researchers have identified a group of ependymal cells with latent regenerative potential in the central nervous system (CNS) of mice. The cells underwent extensive proliferation and differentiation in response to CNS damage in adult mice and were coaxed into differentiating in cell culture when suitable factors were added. If similar cells are identified in humans, this would open new avenues for treating injuries affecting the brain and spinal cord.
The work was published in Developmental Cell (“DNGR-1-tracing marks an ependymal cell subset with damage-responsive neural stem cell potential”). Bruno Frederico, PhD, and Caetano Reis e Sousa, PhD, researchers from the Francis Crick Insitute, led the study.
Stem cells help repair tissue damage by replacing cells after disease or injury. In contrast to some organs, such as the skin and intestine, where stem cells are constantly active, the adult mammalian CNS has limited regenerative potential.
The team of researchers identified a group of CNS cells that express DNGR-1, a receptor that, until now, had only been found on cells of the immune system. “We demonstrate that DNGR-1-lineage-traced ependymal cells arise early in embryogenesis (E11.5) and subsequently spread across the lining of cerebrospinal fluid (CSF)-filled compartments to form a contiguous sheet from the brain to the end of the spinal cord,” the researchers wrote in their paper.
In healthy mice, these DNGR-1-traced cells remained committed to their ependymal fate. However, in injured mouse spinal cords, the cells responded by dividing, migrating towards the damaged area, and differentiating into astrocytes, one of the major cell types of the nervous system.
“[We] don’t know if these cells exist in humans,” Frederico explained. “[But] if they do, it would be interesting to see if they also default to becoming astrocytes rather than neurons in response to damage. This might help explain why the mammalian central nervous system does not have a strong ability to repair itself after injury.
“If we could find a way to overcome the barriers that are stopping the differentiation into neurons and oligodendrocytes after spinal cord injury, it could present a new avenue of therapies to treat spinal cord injuries.”
The team also looked at these cells in detail in the lab and found they demonstrated key hallmarks of stem cell behavior. They divided continuously over a long period of time, and were also able to differentiate into all three main cell types of the central nervous system—neurons, astrocytes, and oligodendrocytes.
“However, whether this means that those cells can be considered latent stem cells remains to be fully established,” the researchers wrote in their paper. “The tri-potency of DNGR-1-traced ependymal cells could only be revealed in vitro, and it will be important to assess why and how differentiation in vivo is restricted to astrocytes.”
But the work represents an important advance in understanding the heterogeneity of ependymal cells and how this particular subset responds to damage in the CNS.
“There was uncertainty over whether ependymal cells can have neural stem cell capabilities, but this study underscores their potential,” Reis e Sousa said. “We hope that studying these cells will help build a more complete picture of the role different types of stem cells play in repairing damage, which could have important implications for regenerative medicine.”