Mesenchymal stem cells regulate blood-brain barrier integrity through TIMP3 release after traumatic brain injury.
Sci Transl Med
; 4(161): 161ra150, 2012 Nov 21.
Article
en En
| MEDLINE
| ID: mdl-23175708
ABSTRACT
Mesenchymal stem cells (MSCs) may be useful for treating a variety of disease states associated with vascular instability including traumatic brain injury (TBI). A soluble factor, tissue inhibitor of matrix metalloproteinase-3 (TIMP3), produced by MSCs is shown to recapitulate the beneficial effects of MSCs on endothelial function and to ameliorate the effects of a compromised blood-brain barrier (BBB) due to TBI. Intravenous administration of recombinant TIMP3 inhibited BBB permeability caused by TBI, whereas attenuation of TIMP3 expression in intravenously administered MSCs blocked the beneficial effects of the MSCs on BBB permeability and stability. MSCs increased circulating concentrations of soluble TIMP3, which blocked vascular endothelial growth factor-A-induced breakdown of endothelial cell adherens junctions in vitro and in vivo. These findings elucidate a potential molecular mechanism for the beneficial effects of MSCs on the BBB after TBI and demonstrate a role for TIMP3 in the regulation of BBB integrity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lesiones Encefálicas
/
Barrera Hematoencefálica
/
Inhibidor Tisular de Metaloproteinasa-3
/
Trasplante de Células Madre Mesenquimatosas
/
Células Madre Mesenquimatosas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Sci Transl Med
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos