Abstract
Human bone marrow-derived mesenchymal stem cells (MSC) home to injured tissues and have regenerative capacity. In this study, we have investigated in vitro the influence of apoptotic and necrotic cell death, thus distinct types of tissue damage, on MSC migration. Concordant with an increased overall motility, MSC migrated towards apoptotic, but not vital or necrotic neuronal and cardiac cells. Hepatocyte growth factor (HGF) was expressed by the apoptotic cells only. MSC, in contrast, revealed expression of the HGF-receptor, c-Met. Blocking HGF bioactivity resulted in significant reduction of MSC migration. Moreover, recombinant HGF attracted MSC in a dose-dependent manner. Thus, apoptosis initiates chemoattraction of MSC via the HGF/c-Met axis, thereby linking tissue damage to the recruitment of cells with regenerative potential.
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Acknowledgments
This work has been supported by a grant from the German Federal Ministry for Education and Research (BMBF, 01GN0951). The authors would like to thank Ms. Nathalie Walter and Heike Löffler for excellent technical assistance. We are grateful to Dr. A. Methner (Department of Neurology, Heinrich Heine University Medical Center, Düsseldorf, Germany) for HT-22 cells and to Prof. Dr. A. Gödecke (Institute of Heart and Circulation Physiology, Heinrich Heine University Medical Center, Düsseldorf, Germany) for HL-1 cells.
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Vogel, S., Trapp, T., Börger, V. et al. Hepatocyte growth factor-mediated attraction of mesenchymal stem cells for apoptotic neuronal and cardiomyocytic cells. Cell. Mol. Life Sci. 67, 295–303 (2010). https://doi.org/10.1007/s00018-009-0183-3
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DOI: https://doi.org/10.1007/s00018-009-0183-3