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Autologous Bone Marrow Mononuclear Cell Therapy for Severe Traumatic Brain Injury in Children

Cox, Charles S Jr MD*; Baumgartner, James E MD*; Harting, Matthew T MD*†; Worth, Laura L MD, PhD§; Walker, Peter A MD*†; Shah, Shinil K DO*†; Ewing-Cobbs, Linda PhD*; Hasan, Khader M PhD‡; Day, Mary-Clare RN, BSN*; Lee, Dean MD, PhD§; Jimenez, Fernando MS*; Gee, Adrian PhD¶

doi: 10.1227/NEU.0b013e318207734c
Research-Human-Clinical Studies
Press Release

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 × 106 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.

CONCLUSION: Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.

*Departments of Pediatric Surgery, †Surgery, and ‡Diagnostic & Interventional Imaging, University of Texas Medical School at Houston, Houston, Texas; Children's Memorial Hermann Hospital, University of Texas, Houston, Texas; §Department of Pediatrics, Division of Cell Therapy, MD Anderson Cancer Center, Houston, Texas; ¶Baylor College of Medicine Center for Cell and Gene Therapy, Houston, Texas

Received, December 18, 2009.

Accepted, May 6, 2010.

Correspondence: Charles S. Cox Jr, MD, 6431 Fannin, MSB 5.236, Houston, TX 77030. E-mail: Charles.S.Cox@uth.tmc.edu

Copyright © by the Congress of Neurological Surgeons