NCE Year 4

The present project aimed at developing a tool and technology in the form of a large animal model to evaluate the potential utility and safety of transplanting motor neurons derived from human embryonic stem cells into the spinal cord of an in vivo research model. The studies used a nerve root injury model that results in loss of motor neurons in the spinal cord, thereby mimicking the effects of a spinal cord injury affecting the most caudal part of the spinal cord or motor neuron disorders such as amyotrophic lateral sclerosis (ALS). Embryonic human stems cell were used to growth early forms of motor neurons in cultures, and the cells were injected into the motor neuron area of the lumbar spinal cord after an avulsion injury of lumbosacral nerve roots. A surgical repair of lumbar nerve roots with surgical re-attachments of the roots to the spinal cord was also performed. In addition, all subjects received treatment with a new combination of immuno-suppression medications to allow for improved survival of human cells in the in vivo research model spinal cord. Animals were evaluated at both 2 and 7 months after the injury, surgical root repair, and transplantation of human motor neurons into the in vivo research model spinal cord spinal cord. All subjects showed excellent survival of human cells, and many of the transplanted cells had also developed synaptic contacts with host nerve cells in the in vivo research model spinal cord spinal cord. Some of the cells also showed nerve transmitter expression suggestive of a motor neuron profile and extension of nerve processes into the repaired ventral roots. Recordings from pelvic floor muscles and bladder pressure recordings confirmed injury effects from the initial nerve root injury but absence of any detectable functional adverse effects. The development of the large animal tool and technology was successful. In future studies, this new tool and technology may be used to assess potential utility and safety of emerging human stem cell therapies to replace degenerating motor neurons.