Hepatocyte growth factor-mediated attraction of mesenchymal stem cells for apoptotic neuronal and cardiomyocytic cells.
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.
Vogel
Sebastian
S
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Moorenstrasse 5, Bldg. 14.80, 40225, Düsseldorf, Germany.
Trapp
Thorsten
T
Börger
Verena
V
Peters
Corinna
C
Lakbir
Dalila
D
Dilloo
Dagmar
D
Sorg
Rüdiger V
RV
D017209:Apoptosis; D002465:Cell Movement; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012038:Regeneration
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met