RT journal article T1 Unraveling the differential mechanisms of revascularization promoted by MSCs & ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia A1 Rojas Torres, Marta A1 Beltrán Camacho, Lucía A1 Martínez Val, Ana A1 Sánchez Gomar, Ismael A1 Eslava Alcón, Sara A1 Rosal Vela, Antonio A1 Jiménez Palomares, Margarita A1 Doiz Artázcoz, Esther A1 Martínez-Torija, Mario A1 Moreno-Luna, Rafael A1 Olsen, Jesper V. A1 Durán Ruiz, María del Carmen A2 BiomedicinaBiotecnología y Salud Pública A2 Cirugía AB AbstractBackground Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral arterydisease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremitiesand elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities.Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization.However, the variability seen in several factors such as cell combinations or doses applied, have limited theirsuccess in clinical trials, being necessary to reach a consensus regarding the optimal “cellular-cocktail” prior furtherapplication into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert theirregenerative properties.Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combinationof endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT),compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI.Methods Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemicmice (after femoral ligation) that received 50 μl of physiological serum alone or a cellular combination of ATMSCswith either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carriedout for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecularchanges in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach.Results AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 dayspost-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group SN 1423-0127 YR 2024 FD 2024-07-15 LK http://hdl.handle.net/10498/35703 UL http://hdl.handle.net/10498/35703 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 08-nov-2026