Subscribe to RSS
DOI: 10.1055/s-2005-861938
Direct intravital fluorescence microscopic analysis of Stromal Cell Derived Factor-1 (SDF-1) mediated stem cell homing
Objectives: Strategies for myocardial regeneration focus on intravascular administration or mobilisation of stem cells (SC). SDF-1 is discussed as homing factor for SC to injured myocardium. We investigated the role of SDF-1 for mediating SC homing using different in vitro and in vivo approaches in the mouse.
Material and Methods: In hearts of C57/BL6J mice the LAD coronary artery was ligated. After 24h SDF-1 cardiac mRNA expression was measured by rtPCR. Chemoattractant activity of SDF-1 (100–500ng/ml) for murine c-kit+ bone marrow SC was studied using Boyden chamber assays (0.2×106 SC in upper chamber). The microvascular bed of right cremaster muscles was topically exposed to SDF-1 (200ng/ml) and studied by intravital fluorescence microscopy upon intra-arterial injection of green-fluorescently labelled SC (2×106 c-kit+). SC rolling was recorded during first pass, while firm adherence of SC to the venular endothelium was assessed after 1h. Values were compared to those in controls without SDF-1-exposure.
Results: SDF-1 mRNA expression was significantly increased 24h after myocardial infarction. In vitro, SC migrated against an SDF-1 concentration gradient in a dose-dependent fashion (20%–75%). In vivo, the fraction of rolling SC increased significantly upon SDF-1 exposure (14±2% vs. control: 6±1% p<0.01). Furthermore, SDF-1 increased firm adhesion of SC (8±4 cells/mm2 vs. controls: 3±1 cells/mm2).
Conclusions: SDF-1 is upregulated after myocardial infarction and is capable to induce dose-dependent cell migration. SDF-1 results in increased stem cell-endothelial cell interactions in vivo even under non-inflammatory conditions. These results warrant further investigations of SDF-1 action in inflammatory environments, such as myocardial ischemia and infarction.