title: Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord.
abstract: BACKGROUND
  Although multiple clinical trials are currently testing different stem cell therapies as treatment alternatives for many neurodegenerative diseases and spinal cord injury, the optimal injection parameters have not yet been defined.
  
  
  OBJECTIVE
  To test the spinal cord's tolerance to increasing volumes and numbers of stem cell injections in the pig.
  
  
  METHODS
  Twenty-seven female Göttingen minipigs received human neural progenitor cell injections using a stereotactic platform device. Cell transplantation in groups 1 to 5 (5-7 pigs in each) was undertaken with the intent of assessing the safety of an injection volume escalation (10, 25, and 50 µL) and an injection number escalation (20, 30, and 40 injections). Motor function and general morbidity were assessed for 21 days. Full necropsy was performed; spinal cords were analyzed for graft survival and microscopic tissue damage.
  
  
  RESULTS
  No mortality or permanent surgical complications were observed during the 21-day study period. All animals returned to preoperative baseline within 14 days, showing complete motor function recovery. The histological analysis showed that there was no significant decrease in neuronal density between groups, and cell engraftment ranged from 12% to 31% depending on the injection paradigm. However, tissue damage was identified when injecting large volumes into the spinal cord (50 μL).
  
  
  CONCLUSIONS
  This series supports the functional safety of various injection volumes and numbers in the spinal cord and gives critical insight into important safety thresholds. These results are relevant to all translational programs delivering cell therapeutics to the spinal cord.
authors.affiliation: *Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia; ‡Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, Georgia; §Department of Neurosurgery, School of Medicine, University of Alabama, Birmingham, Alabama; ¶Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Juanmarco
authors.initials: J
authors.lastname: Gutierrez
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Lamanna
authors.forename: Natalia
authors.initials: N
authors.lastname: Grin
authors.forename: Carl V
authors.initials: CV
authors.lastname: Hurtig
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Miller
authors.forename: Jonathan
authors.initials: J
authors.lastname: Riley
authors.forename: Lindsey
authors.initials: L
authors.lastname: Urquia
authors.forename: Pablo
authors.initials: P
authors.lastname: Avalos
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000818:Animals; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007278:Injections, Spinal; D008845:Microinjections; D058953:Neural Stem Cells / Q000637:transplantation*; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D013556:Swine, Miniature