title: Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results.
abstract: OBJECTIVE
  A Phase I, open-label nonrandomized study was conducted to assess the safety and tolerability of incubated autologous macrophages administered to patients with acute complete spinal cord injury (SCI).
  
  
  METHODS
  This therapy was first tested in rat models of spinal cord transection and contusion, in which it was shown to promote motor recovery. The procedure developed for clinical use consists of isolating monocytes from patient blood and incubating them ex vivo with autologous dermis. The resulting incubated autologous macrophages were injected into the patient's spinal cord immediately caudal to the lesion within 14 days of injury. Patients underwent preoperative and follow-up neurological assessment (American Spinal Injury Association [ASIA] standards), electrophysiological monitoring (motor evoked and/or somatosensory evoked potentials), magnetic resonance imaging, and safety monitoring. Before macrophage administration, complete neurological functional loss (ASIA Grade A) was confirmed in all patients. Of the eight patients in the study, three recovered clinically significant neurological motor and sensory function (ASIA Grade C status). During the study period, some adverse events were encountered, the most serious of which involved two cases of pulmonary embolism and one case of osteomyelitis that were treated and resolved without further complication. These and other adverse events appear to be similar to those encountered in other spinal cord-injured patients and are not considered a consequence of the experimental therapy.
  
  
  CONCLUSIONS
  It is concluded that incubated autologous macrophage cell therapy is well tolerated in patients with acute SCI. Further clinical evaluation is warranted.
authors.affiliation: Department of Neurosurgery, Chaim Sheba Medical Center, Tel-Hashomer, Israel. nachshon.knoller@sheba.health.gov.il
authors.forename: Nachshon
authors.initials: N
authors.lastname: Knoller
authors.forename: Gustavo
authors.initials: G
authors.lastname: Auerbach
authors.forename: Valentin
authors.initials: V
authors.lastname: Fulga
authors.forename: Gabriel
authors.initials: G
authors.lastname: Zelig
authors.forename: Josef
authors.initials: J
authors.lastname: Attias
authors.forename: Ronit
authors.initials: R
authors.lastname: Bakimer
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Marder
authors.forename: Eti
authors.initials: E
authors.lastname: Yoles
authors.forename: Michael
authors.initials: M
authors.lastname: Belkin
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
authors.forename: Moshe
authors.initials: M
authors.lastname: Hadani
mesh_terms: D000208:Acute Disease; D000328:Adult; D018929:Cell Culture Techniques; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D011655:Pulmonary Embolism / Q000209:etiology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome