Spinal Cord Injury Reveals Multilineage Differentiation of Ependymal Cells

PLoS Biology, 2008 · DOI: 10.1371/journal.pbio.0060182 · Published: July 22, 2008

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injuries often lead to lasting functional problems. The spinal cord contains stem cells that, when grown in the lab and then transplanted back into the injured spinal cord, can help recovery, showing these cells can aid regeneration but don't do so effectively on their own. This study demonstrates that most of the stem cell potential in the adult spinal cord comes from ependymal cells, which line the central canal. After a spinal cord injury, these cells not only create scar tissue but also, to a smaller degree, produce oligodendrocytes. Changing the fate of what ependymal cells produce after spinal cord injury could be a different way to replace damaged cells, rather than using cell transplantation.

Study Duration

10 Months

Participants

Mice

Evidence Level

Level 2: Experimental study using transgenic mouse models

Key Findings

1
Close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal.
2
Ependymal cells give rise to a substantial proportion of scar-forming astrocytes as well as to some myelinating oligodendrocytes after spinal cord injury.
3
Ependymal progeny migrated towards the injury site in the dorsal funiculus and an increasing number of recombined cells accumulated in the forming glial scar over several weeks and remained there for at least 10 mo after the insult

Research Summary

The study uses genetic fate mapping to show that ependymal cells lining the central canal of the adult spinal cord act as neural stem cells in vitro and contribute extensively to the glial scar in vivo. Injury induces proliferation of ependymal cells and migration of ependyma-derived progeny towards the site of injury. Ependymal cell progeny differentiate and give rise to astrocytes as well as myelinating oligodendrocytes, making them an attractive candidate population for non-invasive manipulation after injury.

Practical Implications

Cell Replacement Therapies

Modulating the fate of ependymal cell progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies.

Target for Therapeutic Intervention

Ependymal cells are an attractive candidate population for non-invasive manipulation after injury.

Scarring Manipulation

The finding that ependyma-derived progeny is not associated with the main scar-associated axonal growth-inhibiting factor suggests that they may even support some local sprouting.

Study Limitations

1
The study is conducted on mice and may not directly translate to humans.
2
The in vitro conditions may not fully replicate the in vivo environment, potentially affecting stem cell behavior.
3
Recombination was never fully penetrant in the ependymal cells

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