title: Targeted spinal cord therapeutics delivery: stabilized platform and microelectrode recording guidance validation.
abstract: OBJECTIVE
  No validated delivery technique exists for accurate, reproducible delivery of biological therapies to discrete spinal cord targets. To address this unmet need, we have constructed a stabilized platform capable of supporting physiologic mapping, through microelectrode recording, and cellular or viral payload delivery to the ventral horn.
  
  
  METHODS
  A porcine animal model (n = 7) has been chosen based upon the inherent morphologic similarities between the human and porcine spine. Animals underwent physiologic mapping and subsequent microinjection of a green-fluorescent-protein-labeled cell suspension. Sacrifice (t = 3 h) was performed immediately following behavioral assessment.
  
  
  RESULTS
  Histologic analysis has supported our ability to achieve localization to the ipsilateral ventral horn in the spinal cord. Complications included death due to malignant hyperthermia (n = 1), hindlimb dysfunction attributable to epidural hematoma (n = 1), and hindlimb dysfunction attributable to cord penetration (n = 2).
  
  
  CONCLUSIONS
  These results indicate an ability to achieve accurate targeting, but the elevated incidence of neurologic morbidity will require further studies with longer follow-ups that incorporate procedural and equipment modifications that will allow for a reduced number of cord penetrations and will account for observed cardiorespiratory-associated cord movement. These initial results reinforce the challenges of translating biological restorative therapies from small to large animal models and ultimately to humans.
authors: Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA.
authors: Jonathan
authors: J
authors: Riley
authors: John
authors: J
authors: Butler
authors: Kenneth B
authors: KB
authors: Baker
authors: Shearwood
authors: S
authors: McClelland
authors: Qingshan
authors: Q
authors: Teng
authors: Jun
authors: J
authors: Yang
authors: Mary
authors: M
authors: Garrity-Moses
authors: Thais
authors: T
authors: Federici
authors: Nicholas M
authors: NM
authors: Boulis
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000473:pathology / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000295:instrumentation / Q000379:methods*; D002540:Cerebral Cortex / Q000473:pathology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D008839:Microelectrodes; D008845:Microinjections / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D023421:Models, Animal; D051381:Rats; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000473:pathology* / Q000502:physiology*; D013238:Stereotaxic Techniques / Q000009:adverse effects / Q000295:instrumentation*; D013552:Swine