Autologous Bone Marrow Mononuclear Cell Therapy for Severe Traumatic Brain Injury in Children.
by admin on February 7, 2011
Cox CS Jr, Baumgartner JE, Harting MT, Worth LL, Walker PA, Shah SK, Ewing-Cobbs L, Hasan KM, Day MC, Lee D, Jimenez F, Gee A.
From the University of Texas Medical School at Houston, Departments
of Pediatric Surgery, Surgery, Pediatrics, and Diagnostic & Interventional Imaging; Children’s Memorial Hermann Hospital; University of Texas M.D. Anderson Cancer Center, Department of Pediatrics, Division of Cell Therapy; Baylor College of Medicine Center for Cell and Gene Therapy.
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
pre-clinical 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 if autologous BMMNCs are a safe treatment for severe TBI in children.
METHODS: Ten children aged 5-14 years with a post-resuscitation GCS of
5-8 were treated with 6X10 autologous BMMNCs/kg body weight delivered
intravenously within 48 hours after TBI. To determine 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 post-injury, as were
neuropsychologic 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
cerebrospinal fluid (CSF) volumes showed no reduction from 1-6 months
post injury. Dichotomized Glasgow Outcome Score (GOS) at 6 months showed
70% with good outcomes and 30% with moderate to severe disability.
****CONCLUSION: Bone marrow harvest and intravenous
mononuclear cell infusion as treatment for severe TBI in children is
logistically feasible and safe.