title: Cervical multilevel intraspinal stem cell therapy: assessment of surgical risks in Gottingen minipigs.
abstract: METHODS
  Assessment of long-term surgical risks from multiple intraspinal cell injections.
  
  
  OBJECTIVE
  To prove that multilevel-targeted cell injection to the spinal cord can be a feasible and safe procedure.
  
  
  BACKGROUND
  Neural cell transplantation has been proposed as a treatment for a variety of neurologic disorders, including degenerative, ischemic, autoimmune, and traumatic etiologies. Among these diseases, the lack of effective treatment for amyotrophic lateral sclerosis has prompted the search for cell-based neuroprotection or motor neuron-replacement therapies.
  
  
  METHODS
  Fifteen female minipigs, divided into 3 experimental groups, underwent either 5 or 10 unilateral injections of neural stem cells or 10 vehicle injections into the C3-C5 segments of the spinal cord, using a device and technique developed for safe and accurate injection into the human spinal cord. All animals received intravenous Tacrolimus (0.025 mg/kg) BID during the course of the study. Sensory and motor functions as well as general morbidity were assessed for 28 days. Full necropsy was performed and spinal cords were analyzed for graft survival. This study was performed under Good Laboratory Practice conditions.
  
  
  RESULTS
  Neither mortality nor permanent surgical complications were observed within the 28-day study period. All animals returned to preoperative baseline showing full motor function recovery. Graft survival was demonstrated by immunohistochemistry.
  
  
  CONCLUSIONS
  Clinically acceptable neural progenitor survival, distribution, and density were achieved using the number of injections and surgical techniques specifically developed for this purpose.
authors.affiliation: Department of Neurosurgery, Emory University, Atlanta, GA 30322, USA.
authors.forename: Bethwel
authors.initials: B
authors.lastname: Raore
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.forename: Jason
authors.initials: J
authors.lastname: Taub
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Riley
authors.forename: Colin K
authors.initials: CK
authors.lastname: Franz
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kliem
authors.forename: Brooke
authors.initials: B
authors.lastname: Snyder
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.forename: Karl
authors.initials: K
authors.lastname: Johe
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002574:Cervical Vertebrae / Q000473:pathology / Q000601:surgery*; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007278:Injections, Spinal; D007796:Laminectomy / Q000379:methods; D008845:Microinjections; D011183:Postoperative Complications / Q000517:prevention & control; D020127:Recovery of Function / Q000502:physiology; D012307:Risk Factors; D013116:Spinal Cord / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D013552:Swine; D013556:Swine, Miniature