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 106 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.
Keywords: chemokines, myocardial regeneration, cell transplantation, cell recruitment, stromal derived factor-1
Current Pharmaceutical Design
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 106 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.
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Cite this article as:
Schuh Alexander, Konschalla Simone, Kroh Andreas, Schober Andreas, Marx Nikolaus, Sonmez Taha Tolga, Zenke Martin, Sasse Alexander and Liehn A. Elisa, Effect of SDF-1 α on Endogenous Mobilized and Transplanted Stem Cells in Regeneration after Myocardial Infarction, Current Pharmaceutical Design 2014; 20 (12) . https://dx.doi.org/10.2174/13816128113199990443
DOI https://dx.doi.org/10.2174/13816128113199990443 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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