Reconstructing neural circuits using transplanted neural stem cells in the injured spinal cord

Abstract

Traumatic spinal cord injury is one of the most common causes of disability in young adults. Restoring independent ambulation in such patients is considered one of the biggest challenges in regenerative medicine because repair of spinal cord injury involves the complex processes of axonal regeneration, remyelination, and formation of new synaptic connections. In this issue of the JCI, Abematsu et al. report their attempts to rise to this challenge, showing in a mouse model of severe spinal cord injury that spinal neuronal circuits can be restored by neural stem cell transplantation, leading to impressive functional recovery in the hind limbs.

Figure 1. Regeneration of the injured spinal cord by neural stem cell transplantation.

Simplified illustration of longitudinal sections of the spinal cord. Shown are motor projections that control voluntary muscle activity and their response to injury and to stem cell transplantation. (A) Descending corticospinal tract axons innervate directly the lower spinal motor neurons (diamonds), which exit the spinal cord in a segmental manner to innervate voluntary muscles. Motor activity is also modulated and controlled by spinal interneurons and multisynaptic tracts (circles). (B) After severe SCI with discontinuation of most spinal projections, there is a nonpermissive environment (shadowed area) for repair processes. Axonal sprouting from surviving spinal neurons (in red) is mostly inefficient, and very few form new synapses with spinal neurons that reside below the injured area. (C) Neural stem cells transplanted into the injured spinal cord differentiate into glia (blue stars) and neurons (blue hexagons). The glial cells create a permissive environment for regeneration, resulting in increased sprouting of surviving nerve fibers. The transplanted neurons form multiple synaptic connections with surviving neurons and with spinal segments below the lesion, resulting in substantially improved transmission of information through the lesion.