SDF1-a facilitates Lin-/Sca1+ cell homing following murine experimental cerebral ischemia.

BACKGROUND: Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized. METHODS: Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin-/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade. RESULTS: Bone marrow demonstrated a significant increase in Lin-/Sca1+ cell counts at 24 hrs (272 ± 60%; P<0.05 vs sham). Mobilization of Lin-/Sca1+ cells to blood was significantly elevated at 24 hrs (607 ± 159%; P<0.05). Serum SDF1-A levels were significant at 24 hrs (Sham (103 ± 14), 4 hrs (94 ± 20%, p = NS) and 24 hrs (130 ± 17; p<0.05)). Brain SDF1-A levels were significantly elevated at both 4 hrs and 24 hrs (113 ± 7 pg/ml and 112 ± 10 pg/ml, respectively; p<0.05 versus sham 76 ± 11 pg/ml). Following administration of an SDF1-A antibody, Lin-/Sca1+ cells failed to mobilize to peripheral blood following stroke, despite continued up regulation in bone marrow (stroke bone marrow cell count: 536 ± 65, blood cell count: 127 ± 24; p<0.05 versus placebo). Exogenously administered Lin-/Sca1+ cells resulted in a significant reduction in infarct volume: 42 ± 5% (stroke alone), versus 21 ± 15% (Stroke+Lin-/Sca1+ cells), and administration of an SDF1-A antibody concomitant to exogenous administration of the Lin-/Sca1+ cells prevented this reduction. Following stroke, exogenously administered Lin-/Sca1+ FISH positive cells were significantly reduced when administered concomitant to an SDF1-A antibody as compared to without SDF1-A antibody (10 ± 4 vs 0.7 ± 1, p<0.05). CONCLUSIONS: SDF1-A appears to play a critical role in modulating Lin-/Sca1+ cell migration to ischemic brain.

Abstract licence: CC BY

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