%0 Journal Article 
%A Rojas Torres, Marta
%A Beltrán Camacho, Lucía
%A Martínez Val, Ana
%A Sánchez Gomar, Ismael
%A Eslava Alcón, Sara
%A Rosal Vela, Antonio
%A Jiménez Palomares, Margarita
%A Doiz Artázcoz, Esther
%A Martínez-Torija, Mario
%A Moreno-Luna, Rafael
%A Olsen, Jesper V.
%A Durán Ruiz, María del Carmen
%T 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
%D 2024
%@ 1423-0127

%U http://hdl.handle.net/10498/35703
%X Abstract
Background Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery
disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities
and 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 their
success in clinical trials, being necessary to reach a consensus regarding the optimal “cellular-cocktail” prior further
application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their
regenerative properties.
Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination
of 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 ischemic
mice (after femoral ligation) that received 50 μl of physiological serum alone or a cellular combination of ATMSCs
with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried
out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular
changes 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 days
post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group
%~ Universidad de Cádiz