RT journal article
T1 Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia
A1 Beltrán Camacho, Lucía
A1 Jiménez Palomares, Margarita
A1 Rojas Torres, Marta
A1 Sánchez Gomar, Ismael
A1 Rosal Vela, Antonio
A1 Eslava Alcón, Sara
A1 Pérez Segura, María del Carmen
A1 Serrano, Ana
A1 Antequera González, Borja
A1 Alonso Pinero, Jose Angel
A1 González Rovira, Almudena
A1 Extremera García, Mª Jesús
A1 Rodríguez Piñero, Manuel
A1 Moreno Luna, Rafael
A1 Røssel Larsen, Martin
A1 Durán Ruiz, María del Carmen
A2 BiomedicinaBiotecnología y Salud Pública
K1 Critical limb ischemia
K1 Circulating angiogenic cells
K1 Proteomics
K1 Angiogenesis
K1 Arteriogenesis
AB BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.
PB BMC
SN 1757-6512
YR 2020
FD 2020-03
LK http://hdl.handle.net/10498/22727
UL http://hdl.handle.net/10498/22727
LA eng
NO Institute of Health Carlos III, ISCIII; Junta de Andalucia
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026