Targeted spinal cord therapeutics delivery: stabilized platform and microelectrode recording guidance validation

Stereotact Funct Neurosurg. 2008;86(2):67-74. doi: 10.1159/000112426. Epub 2007 Dec 12.

Abstract

Background/aims: 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.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Anterior Horn Cells / pathology
  • Anterior Horn Cells / physiology
  • Behavior, Animal / physiology
  • Cell- and Tissue-Based Therapy / instrumentation
  • Cell- and Tissue-Based Therapy / methods*
  • Cerebral Cortex / pathology
  • Evoked Potentials, Motor / physiology
  • Female
  • Microelectrodes
  • Microinjections / adverse effects
  • Microinjections / instrumentation
  • Microinjections / methods*
  • Models, Animal
  • Rats
  • Reproducibility of Results
  • Spinal Cord / pathology*
  • Spinal Cord / physiology*
  • Stereotaxic Techniques / adverse effects
  • Stereotaxic Techniques / instrumentation*
  • Swine