Regeneration of Completely Transected Spinal Cord Using Scaffold of Poly(D,L-Lactide-co-Glycolide)/Small Intestinal Submucosa Seeded with Rat Bone Marrow Stem Cells

Abstract

Using a complete spinal cord transection model, the present study employed a combinatorial strategy comprising rat bone marrow stem cells (rBMSCs) and polymer scaffolds to regenerate neurological function after spinal cord injury (SCI) of different lengths. SCI models with completely transected lesions were prepared by surgical removal of 1 mm (SC1) or 3 mm (SC3) lengths of spinal cord in the eighth-to-ninth spinal vertebrae, a procedure that resulted in bilateral hindlimb paralysis. A cylindrical poly(D,L-lactide-co-glycolide)/small intestinal submucosa scaffold 1 or 3 mm in length with or without rBMSCs was fitted into the completely transected lesion. Rats in SC1 and SC3 groups implanted with rBMSC-containing scaffolds received Basso-Beattie-Bresnahan scores for hindlimb locomotion of 15 and 8, respectively, compared with ∼3 for control rats in SC1-C and SC3-C groups implanted with scaffolds lacking rBMSCs. The amplitude of motor-evoked potentials recorded in the hindlimb area of the sensorimotor cortex after stimulation of the injured spinal cord averaged ∼100 μV in SC1-C and 10-50 μV in SC3-C groups at 4 weeks, and then declined to nearly zero at 8 weeks. In contrast, the amplitude of motor-evoked potentials increased from ∼300 to 350 μV between 4 and 8 weeks in SC1 rats and from ∼200 to ∼250 μV in SC3 rats. These results demonstrate functional recovery in rBMSC-transplanted rats, especially those with smaller defects. Immunohistochemically stained sections of the injury site showed clear evidence for axonal regeneration only in rBMSC-transplanted SC1 and SC3 models. In addition, rBMSCs were detected at the implanted site 4 and 8 weeks after transplantation, indicating cell survival in SCI. Collectively, our results indicate that therapeutic rBMSCs in a poly(D,L-lactide-co-glycolide)/small intestinal submucosa scaffold induced nerve regeneration in a complete spinal cord transection model and showed that functional recovery further depended on defect length.