Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury
Paul Lu, Camila M. Freria, Lori Graham, Amanda N. Tran, Ashley Villarta, Dena Yassin, J. Russell Huie, Adam R. Ferguson, Mark H. Tuszynski
Paul Lu, Camila M. Freria, Lori Graham, Amanda N. Tran, Ashley Villarta, Dena Yassin, J. Russell Huie, Adam R. Ferguson, Mark H. Tuszynski
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Research Article Neuroscience

Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury

Abstract

We reported previously that neural progenitor cell (NPC) grafts form neural relays across sites of subacute spinal cord injury (SCI) and support functional recovery. Here, we examine whether NPC grafts after chronic delays also support recovery and whether intensive rehabilitation further enhances recovery. One month after severe bilateral cervical contusion, rats received daily intensive rehabilitation, NPC grafts, or both rehabilitation and grafts. Notably, only the combination of rehabilitation and grafting significantly improved functional recovery. Moreover, improved functional outcomes were associated with a rehabilitation-induced increase in host corticospinal axon regeneration into grafts. These findings identify a critical and synergistic role of rehabilitation and neural stem cell therapy in driving neural plasticity to support functional recovery after chronic and severe SCI.

Authors

Paul Lu, Camila M. Freria, Lori Graham, Amanda N. Tran, Ashley Villarta, Dena Yassin, J. Russell Huie, Adam R. Ferguson, Mark H. Tuszynski

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Neural progenitor cells combined with rehabilitation significantly improve functional outcomes.

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Neural progenitor cells combined with rehabilitation significantly impro...
(A) Number of pellets eaten on Montoya staircase task. A generalized estimating equation with Poisson distribution (for counting data) and autoregressive correlation matrix structure for repeated measures showed a significant group by time interaction after treatment (Wald χ2, 228.2, P < 0.01 overall for all groups). Further analysis with generalized estimating equation and post hoc interaction with any 2 groups showed that the neural progenitor cell (NPC) and rehabilitation group differed significantly from the lesion-alone group, with a main effect of condition (Wald χ2, 4.54, P = 0.03) and a condition by time interaction (Wald χ2, 228.2, P < 0.001). There was a trend toward better performance, comparing the lesion and rehabilitation group with the lesion-alone group (Wald χ2, 4.54, P = 0.1); no other group comparisons were significant. Lesion alone, n = 20; lesion and rehabilitation, n = 22; NPC alone, n = 14; and NPC and rehabilitation group, n = 16. (B) Accuracy of pellet retrieval (number of pellets displaced divided by number of pellets eaten). A generalized estimating equation with γ distribution (for percentage data) and autoregressive correlation matrix structure for repeated measures showed a significant group by time interaction after treatment (Wald χ2, 398.2, P < 0.01). Further analysis with generalized estimating equation and post hoc interaction with any 2 groups showed that the NPC and rehabilitation group differed significantly from the lesion-alone group (Wald χ2, 7.15, P < 0.01) and the Lesion-NPC group (Wald χ2, 6.43, P = 0.01), and showed a trend toward better performance against the lesion and rehabilitation group (Wald χ2, 2.77, P = 0.1). There was a trend toward better performance comparing the lesion and rehabilitation group with the lesion-alone group (Wald χ2, 2.47, P = 0.1) as well as lesion and rehabilitation group with the lesion and NPC (Wald χ2, 3.32, P = 0.07); no other group comparisons were significant.