Human bone marrow stem cell populations have been applied for cardiac regeneration purposes within different clinical settings in the recent past. The migratory capacity of applied stem cell populations towards injured tissue, after undergoing specific peri-interventional harvesting
and isolation procedures, represents a key factor limiting therapeutic efficacy. We therefore aimed at analyzing the migratory capacity of human cluster of differentiation (CD) 133+ bone marrow stem cells in vivo after intraoperative harvesting from the sternal bone marrow. Human
CD133+ bone marrow stem cells were isolated from the sternal bone marrow of patients undergoing cardiac surgery at our institution. Migratory capacity towards stromal cell-derived factor-1α (SDF-1α) gradients was tested in vitro and in vivo by intravital fluoresecence
microscopy, utilizing the cremaster muscle model in severe combined immunodeficient (SCID) mice and analyzing CD133+ cell interaction with the local endothelium. Furthermore, the role of a local inflammatory stimulus for CD133+ cell interaction with the endothelium was
studied. In order to describe endothelial response upon chemokine stimulation laser scanning microscopy of histological cremaster muscle samples was performed. SDF-1α alone was capable to induce relevant early CD133+ cell interaction with the endothelium, indicated by the
percentage of rolling CD133+ cells (45.9±1.8% in “SDF-1” vs. 17.7±2.7% in “control,” p<0.001) and the significantly reduced rolling velocity after SDF-1α treatment. Furthermore, SDF-1α induced firm endothelial adhesion
of CD133+ cells in vivo. Firm endothelial adhesion, however, was significantly enhanced by additional inflammatory stimulation with tumor necrosis factor-α (TNF-α) (27.9±4.3 cells/mm2in “SDF-1 + TNF” vs. 2.2±1.1 cells/mm2
in “control,” p<0.001). CD133+ bone marrow stem cells exhibit sufficient in vivo homing towards SDF-1α gradients in an inflammatory microenvironment after undergoing standardized intraoperative harvesting and isolation from the sternal bone marrow.
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Bone marrow stem cell (BMSC);
Stromal cell-derived factor-1α (SDF-1α)
Document Type: Research Article
Reference and Translation Centre for Cardiac Stem Cell Therapy, Department for Cardiac Surgery, University of Rostock, Rostock, Germany
Publication date: 2013-09-11
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