Cell transplantation: stem cells and precursor cells

Stem cells have been used to approach four different therapeutic repair strategies in spinal cord injury (SCI): (1) replacement of lost neurons, (2) replacement of oligodendrocytes to promote remyelination of demyelinated and/or regenerated axons, (3) providing a permissive substrate for axonal regeneration to overcome the intrinsic inhibition of surface molecules, and (4) engendering host repair. The first two strategies involve cell-specific differentiation of engrafted neural cells and the latter two may involve grafted neural or non-neural cells. The preclinical data for all of these approaches is at times contradictory and there is no consensus as to what type of stem cell is optimal to facilitate repair in specific injuries. Remyelination has been the most successful stem cell replacement strategy. Partial lineage restriction and pharmacological and/or genetic manipulation to express additional trophic support or restrict responses to host signals appears necessary for optimal neuronal and oligodendrocytic differentiation. However, these modifications will make their clinical application exceedingly difficult. Effects of grafted stem cells on abrogating host immune responses and engendering intrinsic repair is also a mechanism through which stem cells are likely therapeutically beneficial. While clinical trials with stem cell grafting into the injured spinal cord are ongoing, preclinical studies have yet to define mechanisms of action that can be definitively translated to those clinical approaches.