2026-07-01T09:38:47Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/99812024-09-27T09:38:25Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Zak, Magdalena M.
author
Gkontra, Polyxeni
author
Clemente, Cristina
author
Squadrito, Mario Leonardo
author
Ferrarini, Alessia
author
Mota, Ruben A.
author
Oliver, Eduardo
author
Rocha, Susana
author
Aguero, Jaume
author
Vazquez, Jesus
author
De Palma, Michele
author
Ibáñez, Borja
author
Arroyo, Alicia G
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea
funder
Fundación ProCNIC
2020-05-08T09:37:08Z
2020-05-08T09:37:08Z
2019-07
Hum Gene Ther. 2019; 30(7):839-905
10.1089/hum.2018.194
1557-7422
1043-0342
Human gene therapy
30786776
http://hdl.handle.net/20.500.12105/9981
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.
eng
S1P
VEGFA
Cardiac remodeling
Gene-cell angiotherapy
Myocardial infarction
Oxygen diffusion
Sequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Mice
journal article
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SequentialBone-MarrowCell_2019.pdf
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https://repisalud.isciii.es/bitstreams/3c752506-1883-46fd-abf0-dc00f6bdad30/download
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text/plain
SequentialBone-MarrowCell_2019.pdf.txt