Research ArticleTraumatic Brain Injury

Mesenchymal Stem Cells Regulate Blood-Brain Barrier Integrity Through TIMP3 Release After Traumatic Brain Injury

Science Translational Medicine  21 Nov 2012:
Vol. 4, Issue 161, pp. 161ra150
DOI: 10.1126/scitranslmed.3004660

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Mesenchymal Stem Cells Spill Their Secrets

Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults worldwide and is considered a “silent epidemic” in the United States in both civilian and military populations. Pathological cerebral edema and blood-brain barrier (BBB) permeability are the leading causes of death acutely after TBI with very few therapeutic options. It has been established in animal models that intravenously administered adult bone marrow–derived mesenchymal stem cells (MSCs) are able to ameliorate BBB permeability in mice after TBI. In new work, Menge et al. identify the mechanism responsible for this beneficial effect and identify the mediator as a soluble factor produced by MSCs called TIMP3. In a mouse model of TBI, Menge et al. show that down-regulation of TIMP3 expression in intravenously administered human MSCs abrogates their protective effects on the BBB and endothelial cell stability after TBI. Furthermore, the authors demonstrate that administering intravenous recombinant human TIMP3 alone to mice after TBI can fully recapitulate the protective effects of MSCs on vascular stability and BBB integrity, indicating that TIMP3 may be a key factor regulating integrity of the BBB. Although much more work needs to be done, TIMP3 could be a useful cell-free therapeutic for treating the breakdown of BBB integrity and cerebral edema that occurs after TBI.