Application of developmental principles for spinal cord repair after injury.

Abstract

The superiority of the mammalian central nervous system (CNS) compared with other vertebrates does not involve an advanced capacity for regeneration, and any insult results in irreversible functional loss. Spinal cord injury (SCI) is one example of CNS trauma affecting thousands of individuals, mostly young, each year. Despite enormous progress in our comprehension of the molecular and cellular mechanisms underlying the pathophysiology after SCI, also providing targets for therapeutic interventions, no efficient therapy exists as yet, emphasizing the need for further research. A breadth of studies have demonstrated that, after SCI, principles of development come into play either to promote or to prohibit spontaneous regeneration, and their appropriate manipulation has the potential to contribute towards functional recovery. In this overview, some of the most recent and important studies are discussed.These offer explicitly novel input from the field of development to the field of CNS repair regarding the modification of the inhibitory environment of the injured spinal cord - mainly referring to the glial scar - the activation of endogenous cell populations such as ependymal stem cells and oligodendrocyte precursor cells, and the developmental transcriptional program that is transiently activated in neurons after injury. Furthermore, current advances in stem cell technology are highlighted in terms of refinement and precise design of the appropriate stem cell population to be transplanted, not only for cell replacement but also for modulation of the host environment. As single-dimension applications have not yet proved clinically successful, it is suggested that combinatorial strategies tackling more than one target might be more effective.