Treadmill training improves survival and differentiation of transplanted neural precursor cells after cervical spinal cord injury

•The addition of treadmill training to NPC transplantation increases survival and differentiation of the cell graft 8 weeks after cervical SCI in rats.•The combined treatment with NPC transplantation and treadmill training also leads to increased myelination, tissue sparing and regeneration of descending axonal tracts.•Finally, animals with NPC transplantation and treadmill training show increased functional recovery 8 weeks after cervical SCI. Cervical spinal cord injury (SCI) is a devastating event with often lifelong disability. In absence of good treatment options, stem cell therapy with among others neural precursor cells (NPCs) has been introduced to improve neuroregeneration. However, due to secondary injury cascades, survival and differentiation of transplanted NPCs remain poor. Physical therapy and rehabilitation are important corner stones for patients with SCI and have shown beneficial effects on neuroregeneration in animal models. In our current study, we therefore assessed the effects of treadmill training on the survival and differentiation of transplanted NPCs after cervical SCI in rats. Our findings suggest that survival of NPCs as well as differentiation into neurons and oligodendrocytes can be significantly increased when stem cell therapy is combined with treadmill training. In addition, myelination, regeneration of descending tracts and tissue sparing can be improved, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI.