Induction of Neurogenesis and Angiogenesis in a Rat Hemisection Spinal Cord Injury Model With Combined Neural Stem Cell, Endothelial Progenitor Cell, and Biomimetic Hydrogel Matrix Therapy

Abstract

OBJECTIVES:. Acute spinal cord injury is a devastating injury that may lead to loss of independent function. Stem-cell therapies have shown promise; however, a clinically efficacious stem-cell therapy has yet to be developed. Functionally, endothelial progenitor cells induce angiogenesis, and neural stem cells induce neurogenesis. In this study, we explored using a multimodal therapy combining endothelial progenitor cells with neural stem cells encapsulated in a bioactive biomimetic hydrogel matrix to facilitate stem cell–induced neurogenesis and angiogenesis in a rat hemisection spinal cord injury model. DESIGN:. Laboratory experimentation. SETTING:. University laboratory. SUBJECTS:. Female Fischer 344 rats. INTERVENTIONS:. Three groups of rats: 1) control, 2) biomimetic hydrogel therapy, and 3) combined neural stem cell, endothelial progenitor cell, biomimetic hydrogel therapy underwent right-sided spinal cord hemisection at T9–T10. The blinded Basso, Beattie, and Bresnahan motor score was obtained weekly; after 4 weeks, observational histologic analysis of the injured spinal cords was completed. MEASUREMENTS AND MAIN RESULTS:. Blinded Basso, Beattie, and Bresnahan motor score of the hind limb revealed significantly improved motor function in rats treated with combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy (p < 0.05) compared with the control group. The acellular biomimetic hydrogel group did not demonstrate a significant improvement in motor function compared with the control group. Immunohistochemistry evaluation of the injured spinal cords demonstrated de novo neurogenesis and angiogenesis in the combined neural stem cell, endothelial progenitor cell, and biomimetic hydrogel therapy group, whereas, in the control group, a gap or scar was found in the injured spinal cord. CONCLUSIONS:. This study demonstrates proof of concept that multimodal therapy with endothelial progenitor cells and neural stem cells combined with a bioactive biomimetic hydrogel can be used to induce de novo CNS tissue in an injured rat spinal cord.