Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children
Charles S Cox1, James E Baumgartner, Matthew T Harting
1Department 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
Insights
Autologous bone marrow mononuclear cells (BMMNCs) show promise as a safe treatment for severe traumatic brain injury (TBI) in children. This study found the procedure feasible and well-tolerated, with no significant adverse events observed.
Area of Science:
- Pediatric Neurology
- Regenerative Medicine
- Cellular Therapy
Background:
- Severe traumatic brain injury (TBI) in children leads to significant long-term disability and mortality.
- Current treatments for TBI lack neuroprotective or neuroreparative capabilities.
- Preclinical research indicates bone marrow-derived mononuclear cells (BMMNCs) may offer neuroprotection.
Purpose of the Study:
- To evaluate the safety of using autologous BMMNCs for treating severe TBI in pediatric patients.
- To assess the feasibility and tolerability of bone marrow harvest and cell infusion procedures.
Main Methods:
- Ten children (aged 5-14) with severe TBI received intravenous autologous BMMNCs (6x10^8 cells/kg) within 48 hours of injury.
- Safety was monitored via systemic/cerebral hemodynamics, PELOD scores, hepatic enzymes, lung injury scores, and renal function.
- Neuroimaging (cMRI), neuropsychological, and functional outcomes were assessed at 1 and 6 months post-treatment.
Main Results:
- All ten pediatric patients survived the treatment without harvest-related hemodynamic compromise.
- No infusion-related toxicity was detected based on clinical and laboratory markers.
- cMRI showed no volume reduction in gray matter, white matter, or CSF from 1 to 6 months.
- Glasgow Outcome Score at 6 months indicated 70% good outcomes and 30% moderate to severe disability.
Conclusions:
- Bone marrow harvest and intravenous BMMNC infusion are logistically feasible and safe for treating severe TBI in children.
- The procedure demonstrates potential as a safe therapeutic option for pediatric TBI.
- Further research is warranted to explore the efficacy of BMMNCs in improving functional outcomes for children with TBI.
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.
Conclusion:
Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.
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