You are hereApril 23, 2017 | Bone Marrow Stem Cells
Advancing Bone Marrow Mononuclear Cells as an Effective Treatment for Traumatic Brain Injury
Review of “Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells” from STEM CELLS by Stuart P. Atkinson
Bone marrow mononuclear cells (BMMNCs) represent an easy to access, plentiful, and patient-specific mixed population of monocytes, lymphocytes, and hematopoietic stem and progenitor cells. Bone marrow mononuclear cells also display potentially useful regenerative characteristics and this feature has led to the successful undertaking of Phase 1 trials of adult stroke and pediatric traumatic brain injury [1-3].
Given these successes, the laboratory of Charles S. Cox (University of Texas Medical School at Houston, USA) sought to evaluate the safety, feasibility, and regenerative effects of bone marrow mononuclear cell transplantation in a prospective, single center, dose-escalation trial in adult patients with severe traumatic brain injury .
Could bone marrow mononuclear cells represent an effective treatment for traumatic brain injury?
So what were the trial details?
- Patients enrolled into the trial (See Figure) displayed severe traumatic brain injury without signs of irreversible brain injury
- Bone marrow harvest, isolation of BMMNCs, and intravenously re-infusion took place within 48 hours after injury
- No serious adverse effects noted other than non-clinically-significant mild pulmonary toxicity at the highest cell dose
- BMMNC transplantation mediated structural preservation of critical brain regions, as measured by diffusion tensor imaging magnetic resonance imaging (DTI-MRI)
- Brain regions assessed included the corpus callosum and the corticospinal tract at the level of the brainstem
- Structural preservation correlated with functional and neuropsychological outcomes
- BMMNC transplantation also mediated the downregulation of important inflammatory cytokine biomarkers such as IL-1β and IFN-γ
Overall, the trial suggests that bone marrow mononuclear cell transplantation is safe and feasible and may represent an effective treatment for traumatic brain injury, confirming a previous pediatric trial . Furthermore, these easily isolated cells promoted structural preservation and reduced neuroinflammatory responses in the brain. However, the authors do note shortcomings in their trial design, such as injury heterogeneity and the nonrandomized/unblinded design, although they also note the preparation of a future phase 2b trial to evaluate structural outcomes as the primary endpoint.
- Cox CS, Jr., Baumgartner JE, Harting MT, et al. Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children. Neurosurgery 2011;68:588-600.
- Brenneman M, Sharma S, Harting M, et al. Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats. J Cereb Blood Flow Metab 2010;30:140-149.
- Savitz SI, Misra V, Kasam M, et al. Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol 2011;70:59-69.
- Cox CS, Hetz RA, Liao GP, et al. Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells. STEM CELLS 2017;35:1065-1079.