OLIGODENDROCYTES FROM SPINAL CORD MENINGES: AMPLIFICATION, CHARACTERIZATION AND TRANSPLANTATION IN CONTUSIVE INJURY

Spinal cord injury (SCI) is a single event with devastating effects on the life of patients both in physiological and psychological terms and for which only supportive and damage-limiting interventions are available at the moment. In the last decades, regenerative therapies based on cell transplantation have generated increasing attention as a potential therapeutic approach for degenerative diseases such as spinal cord injury. In addition, the discovery of neural stem cells in the adult central nervous system and the expansion of the knowledge of the mechanisms regulating their fate have increased the expectations for therapeutic application of these cells to spinal cord injury. Indeed, a considerable number of potential cell-based regenerative therapies have reached the stage of clinical trial, but a clear solution has not emerged yet. We have recently shown that the leptomeninges host a cell population with neural stem/progenitor properties both in vitro and in vivo: isolated leptomeningeal cells can be propagated in vitro as neurospheres and induced to differentiate into neurons and oligodendrocytes. Moreover, they have been shown to become activated by injury to both the brain and the spinal cord and to migrate in the parenchyma, where they participate in the reaction to the injury. Considering the easily accessible anatomical location of the meninges, leptomeningeal stem/progenitor cells (LeSCs) represent a potential candidate for regenerative cell therapy for spinal cord injury. With this work, we provide a first evidence that leptomeningeal cells might indeed play a role in regenerative therapies applied to SCI. Considering the pathogenetic role of demyelination in SCI and that remyelination is a promising therapeutic approach, we first developed and optimized a method for efficient in vitro production of LeSCs and differentiation into mature oligodendrocytes; protein and gene expression analysis showed that by the end of the protocol cultured LeSCs acquired both the typical morphology of mature oligodendrocytes and the elevated expression of different myelin-specific genes. In addition, we performed a pilot study of the regenerative potential of LeSCs-derived oligodendrocyte precursors in an animal model of contusive spinal cord injury. In our conditions, cells transplantation was associated with a significant improvement of some of the motor functions, as determined by behavioural evaluation through BBB score and CatWalk gait analysis. This work indicates for the first time that leptomeningeal stem/progenitor cells could represent an asset in both transplantational and pharmacological therapy for spinal cord injury and paves the way to further studies of regenerative medicine in human SCI.