Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche.
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Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche. / Schmidt, Nils-Ole; Koeder, Dennis; Messing, Markus; Mueller, Franz-Josef; Aboody, Karen S; Kim, Seung U; Black, Peter M; Carroll, Rona S; Westphal, Manfred; Lamszus, Katrin.
In: BRAIN RES, Vol. 1268, 2009, p. 24-37.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche.
AU - Schmidt, Nils-Ole
AU - Koeder, Dennis
AU - Messing, Markus
AU - Mueller, Franz-Josef
AU - Aboody, Karen S
AU - Kim, Seung U
AU - Black, Peter M
AU - Carroll, Rona S
AU - Westphal, Manfred
AU - Lamszus, Katrin
PY - 2009
Y1 - 2009
N2 - Endogenous and transplanted neural stem cells (NSC) are highly migratory and display a unique tropism for areas of neuro-pathology. However, signals controlling NSC motility in health and disease are still ill-defined. NSC appear to be intimately associated with the cerebral vasculature and angiogenesis is a hallmark of many neurological disorders. This has led us to investigate the influence of quiescent and angiogenically active human endothelial cells on human NSC migration. In vivo we observed frequent perivascular accumulation of human NSC in the proximity of cerebral microvessels upon induction of angiogenesis by cerebral infusion of vascular endothelial growth factor (VEGF) into the murine brain. We analyzed the in vitro effects of conditioned media from human endothelial cells before and after angiogenic stimulation with VEGF on the migration of human NSC in vitro. Non-stimulated endothelial cells induced a moderate chemotactic migration that was significantly enhanced after angiogenic activation by VEGF. In order to identify cytokines that may function as stimulators of NSC chemotaxis, we screened endothelial cell-conditioned media for the expression of 120 different cytokines. We identified PDGF-BB, RANTES, I-TAC, NAP-2, GROalpha, Ang-2, and M-CSF as endothelial cell-released chemoattractants for human NSC in vitro. VEGF-stimulated cerebral microvascular endothelial cells secreted higher levels of Ang-2 and GROalpha, which in part were responsible for the enhanced chemoattraction of NSC. Our findings support the hypothesis that the angiogenically active microvasculature modulates the local guidance of NSC through endothelial cell-derived chemoattractants.
AB - Endogenous and transplanted neural stem cells (NSC) are highly migratory and display a unique tropism for areas of neuro-pathology. However, signals controlling NSC motility in health and disease are still ill-defined. NSC appear to be intimately associated with the cerebral vasculature and angiogenesis is a hallmark of many neurological disorders. This has led us to investigate the influence of quiescent and angiogenically active human endothelial cells on human NSC migration. In vivo we observed frequent perivascular accumulation of human NSC in the proximity of cerebral microvessels upon induction of angiogenesis by cerebral infusion of vascular endothelial growth factor (VEGF) into the murine brain. We analyzed the in vitro effects of conditioned media from human endothelial cells before and after angiogenic stimulation with VEGF on the migration of human NSC in vitro. Non-stimulated endothelial cells induced a moderate chemotactic migration that was significantly enhanced after angiogenic activation by VEGF. In order to identify cytokines that may function as stimulators of NSC chemotaxis, we screened endothelial cell-conditioned media for the expression of 120 different cytokines. We identified PDGF-BB, RANTES, I-TAC, NAP-2, GROalpha, Ang-2, and M-CSF as endothelial cell-released chemoattractants for human NSC in vitro. VEGF-stimulated cerebral microvascular endothelial cells secreted higher levels of Ang-2 and GROalpha, which in part were responsible for the enhanced chemoattraction of NSC. Our findings support the hypothesis that the angiogenically active microvasculature modulates the local guidance of NSC through endothelial cell-derived chemoattractants.
M3 - SCORING: Zeitschriftenaufsatz
VL - 1268
SP - 24
EP - 37
JO - BRAIN RES
JF - BRAIN RES
SN - 0006-8993
ER -