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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Figure 2

Axonal outgrowth from neural progenitor cell grafts.

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Axonal outgrowth from neural progenitor cell grafts. (A) GFP light-level...
(A) GFP light-level immunolabeling reveals extensive outgrowth of neural progenitor cell (NPC) graft-derived axons into caudal host spinal cord. Dotted lines outline graft within contusive lesion site. Horizontal section; rostral to left. (B and C) Higher-magnification images of boxed areas in A showing (B) large numbers of axons near the graft and (C) a moderate density of axons more distantly. (D and E) GFP-labeled axons extend from the C5 lesion site to C8 level (shown) in both (D) white matter and (E) gray matter. (F and G) Quantification of axon profiles in host white matter and gray matter at C8. There is a trend toward greater numbers of axons in host white matter 3 spinal cord segments caudal to the graft in animals that underwent rehabilitation (± SEM; Student’s 1-tailed t test). Asterisk indicates locations of higher magnification view, and arrows indicate individual axon profiles in host gray matter. NPC graft alone, n = 10; NPC and rehabilitation, n = 11. Scale bar: 1 mm (A); 64 μm (B and C); 31 μm (D and E).