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Sequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Mice.
Journal article

Sequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Mice.

  • Żak MM 1Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Gkontra P 1Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Clemente C 1Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Squadrito ML 2École Polytechnique Federale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
  • Ferrarini A 3Proteomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Mota RA 4Animal Facility, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Oliver E 5Myocardial Pathology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Rocha S 1Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Agüero J 5Myocardial Pathology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Vázquez J 3Proteomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • De Palma M 2École Polytechnique Federale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
  • Ibáñez B 5Myocardial Pathology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • Arroyo AG 1Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
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  • 2019-02-22
Published in:
  • Human gene therapy. - 2019
S1P
VEGFA
cardiac remodeling
gene–cell angiotherapy
myocardial infarction
oxygen diffusion
Animals
Biomarkers
Bone Marrow Cells
Cell- and Tissue-Based Therapy
Disease Models, Animal
Genetic Therapy
Humans
Lysophospholipids
Mice
Myocardial Infarction
Neovascularization, Pathologic
Sphingosine
Vascular Endothelial Growth Factor A
Ventricular Remodeling
English Microvascular dysfunction and resulting tissue hypoxia is a major contributor to the pathogenesis and evolution of cardiovascular diseases (CVD). Diverse gene and cell therapies have been proposed to preserve the microvasculature or boost angiogenesis in CVD, with moderate benefit. This study tested in vivo the impact of sequential delivery by bone-marrow (BM) cells of the pro-angiogenic factors vascular endothelial growth factor (VEGFA) and sphingosine-1-phosphate (S1P) in a myocardial infarction model. For that, mouse BM cells were transduced with lentiviral vectors coding for VEGFA or sphingosine kinase (SPHK1), which catalyzes S1P production, and injected them intravenously 4 and 7 days after cardiac ischemia-reperfusion in mice. Sequential delivery by transduced BM cells of VEGFA and S1P led to increased endothelial cell numbers and shorter extravascular distances in the infarct zone, which support better oxygen diffusion 28 days post myocardial infarction, as shown by automated 3D image analysis of the microvasculature. Milder effects were observed in the remote zone, together with increased proportion of capillaries. BM cells delivering VEGFA and S1P also decreased myofibroblast abundance and restricted adverse cardiac remodeling without major impact on cardiac contractility. The results indicate that BM cells engineered to deliver VEGFA/S1P angiogenic factors sequentially may constitute a promising strategy to improve micro-vascularization and oxygen diffusion, thus limiting the adverse consequences of cardiac ischemia.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/37864
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