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
View: Text | PDF
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

×

Figure 3

Corticospinal regeneration into neural progenitor cell graft.

Options: View larger image (or click on image) Download as PowerPoint
Corticospinal regeneration into neural progenitor cell graft. (A and B) ...
(A and B) Corticospinal axons robustly regenerate into the rostral half of a GFP-expressing neural progenitor cell graft (green). Horizontal section; rostral to left and caudal to right. Corticospinal axons were labeled with red fluorescent protein (RFP). (A) Neural progenitor cell (NPC) and (B) NPC and rehabilitation groups. (C and D) Higher-magnification images of images in A and B, and (E and F) single RFP channel of corticospinal axons. (G and H) Host corticospinal axons (labeled for RFP) regenerating into grafts form bouton-like structures that contain vesicular glutamate transporter 1 (vGlut1, blue) in close apposition to grafted (GFP-expressing, green) cell processes, suggesting synapse formation. (I and J) In host gray matter located 3 spinal cord segments below the lesion, GFP-labeled graft axons also form bouton-like structures that colocalize with the presynaptic marker synaptophysin (Syn, red). (K) Quantification of total corticospinal axon regeneration into NPC grafts normalized to intensity of corticospinal axon labeling in the dorsal columns at C3. There is significantly greater corticospinal regeneration into NPC graft among animals that underwent rehabilitation (P < 0.05, Student’s 1-tailed t test). NPC graft n = 8; NPC and rehabilitation groups, n = 9. Scale bars: 1 mm (A and B); 250 μm (C–F); 30 μm (G); 2 μm (H); 20 μm (I); 4.5 μm (J).