Targeted Microinjection of Cells Into the Ventral Horn Utilizing a Novel Delivery System in Pigs.
John B. Butler MD1, Nicholas Boulis MD1, Dileep Nair MD1, Ken Baker PhD1, Clive Svendsen PhD2, Shearwood McClelland III MD1
1Department of Neurosciences, Lerner Research Institute and Center for Neurological Restoration, Cleveland Clinic Foundation, Cleveland, Ohio
2Waisman Center, University of Wisconsin-Madison
Introduction: Motor neuron diseases such as ALS and SMA, spinal cord injury, demyelinating diseases such as MS all represent devastating diseases of the spinal cord which at this time are treated supportively. Research is focusing on biologic therapies such as in vivo and ex vivo gene therapies, cellular transplants, and viral vectors for engineered protein delivery. Standard strategies for accurate and safe delivery of these therapies do not exist. We have developed a delivery system utilizing a novel platform and injector to functionally map and deliver a biologic payload to a targeted region of the spinal cord.
Methods: 2-level laminectomies were performed on ten pigs for exposure of the lumbar enlargement. We utilized a novel delivery platform to rigidly fix a microdrive and microinjection system over the spinal cord. Utilizing microrecording, evoked potentials and EMG we located the spinal gray matter and ventral horn. After mapping, varied concentrations and volumes of neuroblastoma cells were pumped into the ventral horn at a controlled rate. Post-operatively the pigs were examined, sacrificed, and their spinal cords harvested for histology.
Results: No neurologic deficit was detected post-operatively. Histologic exam of the spinal cords revealed accurate delivery of cells to the ventral horn of the spinal cord with no damage to surrounding neurons or fiber tracts.
Conclusions: Electrophysiological properties of the spinal cord can be used to confirm and guide targeting for the delivery of biological therapeutics. Rigid fixation of the cannula system and controlled pump delivery can be accomplished without detectable neurological deficits.