Bedeutung von stromal cell derived factor-1 (SDF-1) für das »homing« von Stammzellen

Abstract

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. In hearts of C57/BL6J mice the LAD coronary artery was ligated (n=4). After 24 h SDF-1 cardiac mRNA expression was measured by RT-PCR. Chemoattractant activity of SDF-1 (100–500 ng/ml) for murine c-kit⁺ bone marrow SC was studied using Boyden chamber assays (0.2 × 10⁶ SC in upper chamber) (n=3). The microvascular bed of right cremaster muscles was topically exposed to SDF-1 (200 ng/ml) and studied by intravital fluorescence microscopy upon intra-arterial injection of green-fluorescently labelled SC (2 × 10⁶ c-kit⁺) (n=5). SC rolling was recorded during first pass, while firm adherence of SC to the venular endothelium was assessed after 1 h. Values were compared to those in controls without SDF-1-exposure. SDF-1 mRNA expression was significantly increased 24 h 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). 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.