Targeted spinal cord therapeutics delivery: stabilized platform and microelectrode recording guidance validation.
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.
Riley
Jonathan
J
Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA.
Butler
John
J
Baker
Kenneth B
KB
McClelland
Shearwood
S
Teng
Qingshan
Q
Yang
Jun
J
Garrity-Moses
Mary
M
Federici
Thais
T
Boulis
Nicholas M
NM
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