title: Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children.
abstract: BACKGROUND
  Severe traumatic brain injury (TBI) in children is associated with substantial long-term morbidity and mortality. Currently, there are no successful neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer neuroprotection.
  
  
  OBJECTIVE
  To determine whether autologous BMMNCs are a safe treatment for severe TBI in children.
  
  
  METHODS
  Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6×10 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics were monitored during bone marrow harvest; infusion-related toxicity was determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic enzymes, Murray lung injury scores, and renal function. Conventional magnetic resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were neuropsychological and functional outcome measures.
  
  
  RESULTS
  All patients survived. There were no episodes of harvest-related depression of systemic or cerebral hemodynamics. There was no detectable infusion-related toxicity as determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal function. cMRI imaging comparing gray matter, white matter, and CSF volumes showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome Score at 6 months showed 70% with good outcomes and 30% with moderate to severe disability.
  
  
  CONCLUSIONS
  Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.
authors.affiliation: Department of Pediatric Surgery, University of Texas Medical School at Houston, and Children's Memorial Hermann Hospital, University of Texas, Houston, Texas 77030, USA. Charles.S.Cox@uth.tmc.edu
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
authors.forename: James E
authors.initials: JE
authors.lastname: Baumgartner
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Harting
authors.forename: Laura L
authors.initials: LL
authors.lastname: Worth
authors.forename: Peter A
authors.initials: PA
authors.lastname: Walker
authors.forename: Shinil K
authors.initials: SK
authors.lastname: Shah
authors.forename: Linda
authors.initials: L
authors.lastname: Ewing-Cobbs
authors.forename: Khader M
authors.initials: KM
authors.lastname: Hasan
authors.forename: Mary-Clare
authors.initials: MC
authors.lastname: Day
authors.forename: Dean
authors.initials: D
authors.lastname: Lee
authors.forename: Fernando
authors.initials: F
authors.lastname: Jimenez
authors.forename: Adrian
authors.initials: A
authors.lastname: Gee
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000379:methods*; D001930:Brain Injuries / Q000175:diagnosis* / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D016896:Treatment Outcome