Study Design: Multicenter, randomized, blinded, placebo controlled, Bayesian adaptive dose escalation design. Study Intervention: Single dose administered within 48 hours from time of injury. Controls will undergo a sham harvest and receive similarly labeled/external appearance and volume of 0.9% NaCl. BMMNC's will be harvested and undergo processing under cGMP conditions to obtain 6x10^6 cells/kg or 10x10^6 cells/kg weight. The cellular product/placebo will be infused within 48 hours of injury. Safety Monitoring & Follow-Up: Subjects will be monitored for infusion related toxicity post-infusion through hospital discharge and follow-up return study visits. Laboratory and imaging studies will be repeated at the 1, 6, and 12-month follow-up visits. A medical safety monitor (MSM) will review blinded SAE reports following post-infusion Day 14 for each subject in real time to ensure good clinical practice and to quickly identify safety concerns. The MSM will remain blinded to the treatment assignment, unless the NINDS appointed DSMB approves unblinding.
Inclusion Criteria: 1. Between 5 and 17 years of age on the day of injury, 2. Glasgow Coma Score (GCS) between 3 and 8, (best un-medicated post-resuscitation score during screening), 3. Ability to obtain legally authorized representative (LAR) consent, and complete the BMMNC/Sham harvest and cell/placebo infusion within 48 hours of the initial injury, 4. Ability to speak English or Spanish. Exclusion Criteria: 1. Known history of: a. previous brain injury, b. intellectual deficiency or psychiatric condition, defined as inability to independently function in a regular classroom that may invalidate our ability to assess post-injury changes in cognition or behavior (ADHD and/or other learning disabilities are NOT an exclusion), c. neurologic impairment and/or deficit, d. seizure disorder requiring anti-convulsant therapy, e. recently treated infection, f. renal disease or altered renal function (post-resuscitation serum creatinine > 1.5 mg/dL), g. hepatic disease or altered liver function (post-resuscitation, non-contusion related SGPT > 150 μ/L and/or T. Bilirubin >1.3 mg/dL), h. cancer, i. immunosuppression as defined by WBC < 3, 000 cells/ml at admission, j. HIV+, k. chemical or ETOH dependency, l. history of child abuse, m. premature birth (<37 weeks GA/2500 grams) resulting in cognitive/physical disabilities and/or developmental delay. 2. Obliteration of perimesencephalic cistern on initial head CT/MRI suggesting prolonged hypoxic ischemic insult/herniation syndrome. 3. Initial hospital ICP > 40 mm Hg. 4. Hemodynamic instability at the time of screening defined as SBP <90 mmHg, ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normal for age - does not include CPP based inotropic support. IVF alone does not exclude from enrollment. 5. Uncorrected coagulopathy at the time of bone marrow harvest defined as INR > 1.6, PTT > 38 sec; PLT< 100,000; Fibrinogen < 100 g/dL. 6. Unstable pelvic fractures defined as requiring early operative fixation. 7. Pulmonary contusions defined as a chest x-ray with non-anatomic opacification and/or PaO2:FiO2 ratio < 250 associated with the mechanism of injury. 8. Greater than AAST Grade 3 solid or hollow visceral injury of the abdomen and/or pelvis as diagnosed by CT or other imaging. 9. Spinal cord injury diagnosed by CT/MR imaging or clinical findings. 10. Persistent hypoxia defined as SaO2 < 94% for > 30 minutes occurring at any time from hospital admission to time of consent. 11. Positive pregnancy test, if applicable. 12. Concurrent participation in an interventional drug/device research study. 13. Unwillingness to return for follow-up visits. 14. Contraindications to MRI. 15. Penetrating brain injury.