Regenerative Rehabilitation and Stem Cell Therapy Targeting Chronic Spinal Cord Injury: A Review of Preclinical Studies

Stem cell medicine has led to functional recovery in the acute-to-subacute phase of spinal cord injury (SCI), but not yet in the chronic phase, during which various molecular mechanisms drastically remodel the tissue and render it treatment-resistant. Researchers are attempting to identify effective combinatorial treatments that can overcome the refractory state of the chronically injured spinal cord. Regenerative rehabilitation, combinatorial treatment with regenerative medicine that aims to elicit synergistic effects, is being developed. Rehabilitation upon SCI in preclinical studies has recently attracted more attention because it is safe, induces neuronal plasticity involving transplanted stem cells and sensorimotor circuits, and is routinely implemented in human clinics. However, regenerative rehabilitation has not been extensively reviewed, and only a few reviews have focused on the use of physical medicine modalities for rehabilitative purposes, which might be more important in the chronic phase. Here, we summarize regenerative rehabilitation studies according to the effector, site, and mechanism. Specifically, we describe effects on transplanted cells, microstructures at and distant from the lesion, and molecular changes. To establish a treatment regimen that induces robust functional recovery upon chronic SCI, further investigations are required of combinatorial treatments incorporating stem cell therapy, regenerative rehabilitation, and medication.

Automated summary

Stem cell medicine has shown promise in functional recovery for acute-to-subacute spinal cord injury, but faces challenges in the chronic phase. Researchers are exploring combinatorial treatments to overcome the treatment-resistant state of chronically injured spinal cords. Regenerative rehabilitation, which combines regenerative medicine with rehabilitation, has gained attention for its safety and ability to induce neuronal plasticity. However, there is a lack of comprehensive reviews on regenerative rehabilitation, particularly regarding the use of physical medicine modalities in the chronic phase. Further investigations on combinatorial treatments incorporating stem cell therapy, regenerative rehabilitation, and medication are needed for robust functional recovery in chronic spinal cord injury.