Title:Effect of SDF-1 α on Endogenous Mobilized and Transplanted Stem Cells in Regeneration after Myocardial Infarction
Volume: 20
Issue: 12
Author(s): Alexander Schuh, Simone Konschalla, Andreas Kroh, Andreas Schober, Nikolaus Marx, Tolga Taha Sonmez, Martin Zenke, Alexander Sasse and Elisa A. Liehn
Affiliation:
Keywords:
chemokines, myocardial regeneration, cell transplantation, cell recruitment, stromal derived factor-1
Abstract: Aim of the presented study was to investigate the role of stromal derived factor 1 (SDF-1) in mobilizing stem cells in combination
with endothelial progenitor cell (EPC) transplantation in a regenerative strategy for myocardial infarction therapy in a murine
ischemia/reperfusion model.
Initially bone marrow was eradicated and reconstituted with the use of green fluorescent protein (GFP) labelled allogenic cells. After reconstitution,
myocardial ischemia was induced by temporary ligation of the left anterior descending coronary artery (LAD) in C57/B16
mice and maintained for 1h. After reperfusion, EPCs (1 x 10
6 cells) or medium were injected directly into the border zones of the infarcted
areas. In addition, the animals were divided in groups treated or not with specific antibodies against SDF-1α.
4 weeks after transplantation, echocardiography revealed a significantly decreased left ventricular function after application of EPCs in
anti-SDF-1α treated animals compared to untreated groups. Histology revealed that EPC transplantation and anti-SDF-1α treatment diminished
the amount of intramyocardially attracted GFP positive bone marrow cells. Interestingly, no significant changes in the density
of CD31+ vessel structures compared to EPC transplantation alone were detectable in anti-SDF-1α treated groups. Anti-SDF-1α treatment
also increased numbers of inflammatory cells (monocytes and neutrophiles) in infarcted areas. Rate of apoptotic cells and proliferation
after transplantation did not differ.
In conclusion, transplanted endothelial progenitor cells as well as SDF-1α are key factors in mobilization of endogenous bone marrow
cells towards infarcted myocardium. Anti-SDF-1α treatment leads to a significant decreased left ventricular function, alters the inflammatory
processes, but does not lead to significant alterations in neovascularization or collagen content of infarcted areas.
