Transplantation of embryonic spinal cord derived cells to prevent muscle atrophy after various peripheral nerve injuries

Abstract

Every human has 45 miles long nerve network that together with the spinal cord is susceptible to traumatic injuries, leading to a loss of motor and sensory functions. Different surgical repairs are available for peripheral nerve injuries happening on either distal or proximal site. However, the speed of axonal regeneration after the repair is limited and therefore, target muscles atrophy severely during that time, making them incapable of receiving axons after too long time. Neuronal replacement strategy through cell transplantation is a potential method to prevent muscle atrophy. In our study, we tested E14.5 rat embryonic spinal cord derived fetal cells versus neural progenitor cells (NPCs), as well as cells from 3 different spinal cord segments, for their ability to reduce the muscle atrophy after the complete musculocutaneous nerve transection. We showed that fetal cells were more efficient compared to the NPCs, whereas lumbar cells were slightly better compared to thoracic and cervical cells. Therefore, fetal lumbar cells were next used in clinically more relevant injury models that included delayed surgical repair. After long-term crush injury, these cells helped to preserve the muscles, resulting in an earlier functional recovery, while no effect was seen after the nerve transection with delayed end-to-end repair. Next, spinal root avulsion injury that includes the damage to both PNS and CNS, was used. Here, these cells slightly prevented the muscle atrophy, resulting in earlier and better functional recovery after the delayed ventral root reimplantation, while GDNF treatment helped the host motoneuron cell bodies to survive.