Delivery of injectable thermo-sensitive hydrogel releasing nerve growth factor for spinal cord regeneration in rat animal model

Abstract

The main goal of this study was to explore the beneficial effect of nerve growth factor (NGF)-overexpressing of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated in injectable chitosan/β-glycerophosphate/hydroxyethylcellulose (CS/β-GP/HEC) hydrogel for spinal cord regeneration. The CS/β-GP/HEC hydrogel and genetically transduced hADSCs using pseudo-lentiviruses-NGF were prepared. The mechanical properties, morphology and cytotoxicity of the hydrogel were investigated by rheometry, scanning electron microscope (SEM), and MTT assay, respectively. Rats animals were undergone spinal cord injury (SCI), then one-week post-injury, CS/β-GP/HEC hydrogel, transduced hADSCs and transduced hADSCs/CS/β-GP/HEC hydrogel injected into the site of the lesion. Animals with SCI and animals with laminectomy without SCI were considered as negative control and sham groups, respectively. Positive control group received no surgical intervention. At eight weeks post-injection, histological studies indicated a significant increase in cell proliferation, a smaller cavity in size at the SCI site as well as better locomotor functions for transduced hADSCs/CS/β-GP/HEC hydrogel group (P ≤ 0.05) compared to other experimental groups. Our results showed that CS/β-GP/HEC hydrogel in combination with transduced-hADSCs is able to successfully regenerate SCI. These results may be applicable in the selection of the best therapeutic strategy based on gene therapy and tissue engineering for SCI treatment.