Chemokine induced migration of human mesenchymal stem cells: A strategy for directing cardiac repair

Abstract Introduction: The mechanism by which bone marrow stem cells target an area of cardiac injury following myocardial infarction is unknown. Our hypotheses were: [1] granulocyte colony-stimulating factor (G-CSF) enhances the migration of human mesenchymal stem cells (hMSC) towards the chemokine, stromal-derived factor (SDF-1), and [2] CXCR4, the receptor for SDF-1, is required for the hMSC migration. SDF-1 and G-CSF are released during a myocardial infarction, and thus may play a role in stem cell mobilization and attraction. Methods: Migration assays were performed in dual-chamber culture wells containing 8-micron pore size matrigel inserts. SDF-1 was placed in the bottom chamber in all wells except for the control. Sternal bone marrow derived hMSCs were plated into upper chambers containing serum-free medium with and without G-CSF. After 24 hours, migrated cells were isolated and quantified using fluorescent staining. Membrane phenotyping was performed by immunofluorescence using a panel of monoclonal antibodies. Results: hMSC migration in response to SDF-1 was 11.4%(p Conclusions: Exposing hMSCs to G-CSF can significantly enhance the homing capacity of these stem cells towards SDF-1. This chemoattraction did not require the SDF-1 receptor, CXCR4. Ongoing experiments suggest G-CSF may have enhanced stem cell migration through an interaction with the CD44(+) receptor, a homing cell adhesion molecule. Directing and amplifying the homing of endogenous stem cells, using pro-inflammatory chemokines, is a promising therapeutic strategy for reengineering the damaged myocardium.