The consequences of acute and chronic nerve root injury can be devastating to the patient, their immediate support system, as well as to the entire health care system. In addition to functional motor disability, people suffering from nerve root injury develop multiple secondary complications such as pain, weakness, and fatigue, which are closely linked to decreased social and mental health functioning. Treatments designed to mitigate the extent of nerve injury have met with only modest success, and work with mesenchymal stem cells (MSC) has recently shown some promise.
To that end, the work of Spejo et al (Neuroscience 2013, 250: 715-732), examining the protective role of MSC on spinal motoneurons following ventral root crush (VRC) injury, is timely and significant. While ventral root avulsion (VRA) is known to result in 80-90% of neuronal death within two weeks post-injury because of a complete disconnect of neurotrophic factor transport, VRC injury is less well characterized, but much more common in clinical practice. Because the Schwann cell basal membrane and epi- and perineural tissue that surround nerve fibers are preserved with VRC, a guiding scaffold remains to help with the regenerative process. Spejo et al postulated that in this setting, MSC introduced within the spinal cord would improve axonal regeneration by modulating the pro-inflammatory response, reducing inhibitory effects of glial scar, and supplying growth factors that contribute to cell survival, thereby promoting a permissive environment for axonal extension.
Spejo et al utilized 30 adult, 7-week old female Lewis rats, and divided them into 3 VRC groups: crushing alone (n = 5), crushing + DMEM injection in the gray/white matter interface (Dulbeco’s modified eagle medium) (n = 5), and crushing + MSC injection in the gray/white matter interface (n = 5). Two survival times were analyzed: 4 weeks and 12 weeks after crush. They found that compared to the DMEM group, the MSC-treated group had improved motor function recovery in the immediate post-operative period. Also, 4 weeks after injury, an increased motoneuron survival (70 vs 50% in the DMEM group) was observed in the MSC group, coupled with a smaller decrease of inputs at the motoneuron surface and nearby neuropil, seen by synaptophysin and synapsin immunolabeling, and decreased astrogliosis, seen by GFAP immunolabeling. In other words, the SMC group had significant preservation of GABAergic terminals, and relative protection from glutamate excitotoxicity. As a whole, they found that MSC administration within the spinal cord after VRC results in a decreased rate of neuron death, increases in inhibitory synapses, and results in increased number of regenerated axons in comparison to the DMEM-treated control.
While these results are very encouraging, their translation into clinical practice is limited. An isolated acute nerve crush injury is rare, and immediate infusion of patient-derived MSC is not realistic currently. Despite this, the work of Spejo et al contributes to the existing body of literature that suggests a promising role of MSC in the treatment of nerve injury, and can hopefully lead to a better understanding of how nerve injury recovery works.