Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axis
| Autor: | Rebekka Fischer, Marc-Michael Zaruba, Stefan Brunner, Yordan Vanchev, Michael Gröbner, Hans D. Theiss, Christoph Rischpler, M. Hacker, Josef Mueller-Hoecker, Lisa Krieg, Gerald Assmann, Bruno C. Huber, Wolfgang-Michael Franz, Markus Vallaster, Timm Wollenweber |
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| Rok vydání: | 2011 |
| Předmět: |
Benzylamines
Receptors CXCR4 medicine.medical_treatment Dipeptidyl Peptidase 4 Myocardial Infarction Neovascularization Physiologic Antigens CD34 Biology Pharmacology Cyclams CXCR4 Models Biological Neovascularization Mice Heterocyclic Compounds Granulocyte Colony-Stimulating Factor medicine Animals Myocardial infarction Hematopoietic Stem Cell Mobilization Medicine(all) Dose-Response Relationship Drug General Medicine Stem-cell therapy Cell Biology medicine.disease Survival Analysis Chemokine CXCL12 Perfusion Proto-Oncogene Proteins c-kit medicine.anatomical_structure Immunology Heart Function Tests Leukocyte Common Antigens Bone marrow Stem cell medicine.symptom Oligopeptides Homing (hematopoietic) Stem Cell Transplantation Developmental Biology |
| Zdroj: | Stem Cell Research. 7(3):244-255 |
| ISSN: | 1873-5061 |
| DOI: | 10.1016/j.scr.2011.05.003 |
| Popis: | Background G-CSF based stem cell mobilization and stabilization of cardiac SDF-1 by DPP-IV-inhibition (dual stem cell therapy) improve heart function and survival after myocardial infarction. However, it is barely understood whether this new approach acts specifically through the SDF-1/CXCR4 axis, stimulation of resident cardiac stem cells and improved myocardial perfusion. Therefore, we aimed to clarify the role of the SDF1/CXCR4 axis with respect to the benefits of a dual stem cell based therapy. Methodology/principal findings After surgically induced ligation of the LAD, SDF-1/CXCR4 interactions were specifically blocked by the CXCR4 receptor antagonist AMD3100 in G-CSF and Diprotin A treated C57BL/6 mice. G-CSF + DipA treated and non-treated animals served as controls. Because AMD3100 is known to mobilize bone marrow derived stem cells (BMCs) in high concentrations, the optimal dosage (1.25 mg per kg body weight) sufficient to block CXCR4 without stimulating mobilization was established. AMD3100 treatment of G-CSF and Diprotin A stimulated mice significantly decreased myocardial homing of circulating stem cells (FACS analysis) and inverted the beneficial effects of (i) cardiac remodeling (histological analyses), (ii) heart function (Millar tip catheterization) and (iii) survival (Kaplan–Meier curves). G-CSF treatment in combination with DPP-IV inhibition enhanced neovascularization at the infarct border zone which was related to an improved myocardial blood flow as measured by SPECT. Moreover, dual stem cell treatment effectively stimulated the pool of resident cardiac stem cells (FACS) which was reversed by AMD3100 treatment. Conclusions/significance Our data give final proof that homing through the SDF-1/CXCR-4 axis is essential for the success of dual stem cell therapy. |
| Databáze: | OpenAIRE |
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