Implantation of neurotrophin gene modified bone derived mesenchymal stem cells to repair spinal cord complete transection injury in adult rats

Recovery from spinal cord injury (SCI) after mesenchymal stem cells (MSCs) implantation is minimal due to the limited capacity for the reduction in the cystic cavitation, the axonal regeneration, and neural plasticity in the spinal cord. We combined MSC implantation with neurotrophin gene therapy in an attempt to enhance regeneration and functional recovery after thoracic spinal cord complete injury in adult rats. Primary MSCs were transfected with reconstructed vectors encoding rat brain-derived neurotrophic factor (BDNF) or human neurotrophin-3 (NT-3). MSCs expressing BDNF or NT-3 or both were implanted into the transected spinal cord of rats. Enhanced regenerative sprouting of the fibers and recovery of hind limb function was observed in rats implanted with MSCs expressing BDNF and NT-3. Efficiency of the treatment was improved in dual combination of BDNF and NT-3 in MSCs. This combined neurotrophin genetic engineering of MSCs not only resulted in cells that were more effective in promoting axonal outgrowth but could also lead to enhanced recovery after SCI. Cell transplantation combined with two gene therapy provides better effect in the restoration of SCI.