DHAM-BMSC Matrix Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury in Adult Rats

Abstract

Axonal regeneration and functional recovery after complete spinal cord injury (SCI) are limited in adult mammals. The purpose of this study was to investigate whether an innovative composite matrix made from a denuded human amniotic membrane (DHAM) seeded with bone marrow stromal cells (BMSCs) could promote axonal regeneration after SCI. We transplanted the composite matrix between the stumps of severed spinal cords immediately following SCI. Twelve weeks after surgery, the functional recovery of the hindlimbs of operated rats was evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating score and the cold spray test. Axonal regeneration was examined with anterograde and retrograde tracing techniques. Electrophysiological analysis was used to evaluate the improvement in neuronal circuits. Immunohistochemistry was employed to identify local injuries and their recovery. Our results showed that functional recovery was significantly improved in the DHAM-BMSC-transplanted group. Histological studies revealed that host axons grew back into the spinal cord under the composite matrix, and many BMSCs were found in the lesion sites, with some being neurofilament-H (NF-H)-positive, suggesting the possible differentiation of BMSCs into neural-like cells. Furthermore, the restoration of anatomical connections across the injury sites was positively correlated with the recovery of spinal cord conductivity and function in the DHAM-BMSC group. These findings indicate that the DHAM-BMSC composite matrix is a promising therapeutic approach for promoting axonal regeneration and repair SCI.