Spinal cord injuries, resulting in permanent disability or paralysis in most cases, account for around eleven thousand new cases in the US, annually. Due to the lack of effective treatment strategies, it is considered as the most devastating of all traumatic conditions. Now, a recent study published in the journal Stem Cells reports that activation of ependymal stem/progenitor cells from injured spinal cord (epSPCi), using endogenous stem cell-associated mechanisms, may aid in rescuing neurological function, thereby reversing paralysis associated with spinal cord injuries.

The ability of ependymal cells to differentiate into oligodendrocytes and other cell types essential for restoring neuronal function, after the proliferation and migration of the specific cells to the injured area, makes it an efficient therapeutic target to improve recovery after injury. The study, headed by Victoria Moreno-Manzano from Centro de Investigación Príncipe Felipe, Valencia, Spain, showed that the proliferation of epSPCi stem cells, recruited to the injured area, can be regulated through innate and adaptive immune responses. Also, the specific stem cells cultured from the rat models of spinal cord injury demonstrated enhanced self-renewal and proliferation that is ten times faster than the epSPC obtained from healthy control animals. Further, genetic profile analysis showed a significant influence of inflammation on signaling in the cells after the injury, including the up-regulation the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and the mitogen-activated protein kinase (MAPK) pathways.

Neurospheres obtained from both epSPC and epSPCi showed efficient differentiation into functional spinal motoneurons and oligodendrocytes, which is crucial for producing myelin sheath and providing support to axons. However, a consistent and higher yield of differentiated cells was found with epSPCi cultures. Substantial recovery of activity was observed in the rat model after one week of severe spinal cord contusion following the acute transplantation of undifferentiated epSPCi or the resulting oligodendrocyte precursor cells. The researchers also noticed the ability of the transplanted cells to migrate long distance from the rostral and caudal regions of the graft to the neurofilament-labelled axons within and around the lesion zone.

Earlier, Meletis, et al. (PLoS Biol, 2008) suggested the feasibility of using genetically modulated ependymal cells as an effective treatment strategy for spinal cord injury. Using genetic fate mapping, the researchers found that the neural stem cells in the adult spinal cord reside in ependymal cells that form a thin membrane lining the inner-brain ventricles and the central canal of the spinal cord. The researchers also concluded on the regulation of ependymal cells, recruited following a spinal cord injury, as an effective alternative for cell transplantation therapies in spinal cord injury.

Some of the common treatment options for spinal cord injury include high doses of methylprednisolone administered within 8 hours of injury, brace for spinal realignment, and intubation in cases with respiratory complications. Several researches are underway to develop effective treatment strategies aimed at alleviating the paralyzing effect of the injury and enhancing regrowth of nerve fibers to resume the neurological function.

The current study, suggesting modulation of endogenous ependymal cells to reverse paralysis, holds great potential to emerge as a viable cell-based regenerative therapy for debilitating spinal-cord injuries.

References

1. Moreno-Manzano V, Rodríguez-Jiménez FJ, García-Roselló M. Activated Spinal Cord Ependymal Stem Cells Rescue Neurological Function. Stem Cells. 2009 Jan 28. [Epub ahead of print].

2. Meletis K, Barnabé-Heider F, Carlén M, et al. Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol. 2008 Jul 22;6(7):e182.