Transplantation of Neuregulin1-Overexpressing Bone Marrow Mesenchymal Cells Accelerates Motor Functional Recovery by Facilitating Neurite Outgrowth and Reducing Cell Apoptosis in Rat after Spinal Cord Injury

Abstract

Background: Bone marrow mesenchymal stem cells (BMSCs) transplantation offers an attractive strategy for treating multiply neurological diseases. Neuregulin1 (NRG1) plays fundamental roles in nervous system development and nerve repair. In this study, we aimed to investigate whether transplantation of NRG1-overexpressing BMSCs could alleviate spinal cord injury (SCI), and to explore the possible underling mechanisms. Methods: In vitro, NRG1-overexpressing BMSCs were constructed via plasmid transfection, and co-cultured with PC12 cells subjected to oxygen-glucose deprivation (OGD). Neurite outgrowth, cell viability and apoptosis of PC12 cells were evaluated. In vivo, BMSCs, empty-vector BMSCs and NRG1-overexpressing BMSCs were transplanted respectively into rats with SCI. Rat locomotor functions, neuronal chromatolysis, neurite outgrowth and cell apoptosis were assessed respectively. Results: The results showed that NRG1-overexpressing BMSCs in vitro significantly expedited neurite growth, elevated growth-associated protein 43 expression, enhanced cell viability and rescued ODG-induced apoptosis in PC12 cells. In vivo, transplantation of NRG1-overexpressing BMSCs notably accelerated rat motor functional recovery, attenuated neuronal chromatolysis, promoted neurite outgrowth and reduced cell apoptosis after SCI. Moreover, NRG1-overexpressing BMSCs were also able to regulate apoptosis-related proteins expression after SCI. Conclusions: These findings demonstrate that NRG1-overexpressing BMSCs can accelerate motor functional recovery by facilitating neurite outgrowth and reducing cell apoptosis after SCI, suggesting that NRG1-overexpressing BMSCs may be a promising candidate for the treatment of SCI.