1:Universidad de Cádiz; 2:Instituto de innovación e investigación biomédica de Cádiz

Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease, and it is characterized by a chronic obstruction of the major systemic arteries. This debilitating disease affects over millions of people around the world. To date, the treatment available is surgical revascularization and, although many advances have been made in this approach, high percentage of CLTI patients cannot undergo surgery, mainly due to associated comorbidities. As an alternative, angiogenic cell therapy has arisen as a promising, safe and feasible strategy applicable to ischemic diseases. However, before any clinical translation, determining the route-dependent bio-distribution of the injected cells within the organism is crucial. In this sense, lipophilic DiR dye labelling allows a simple and quick detection of cells once administered, being compatible to in vivo imaging systems. Herein, a comparative study using pre-labelled endothelial colony forming cells (ECFCs) injected through different routes in a murine model of CLTI is shown, with the aim of evaluating the most suitable administration strategy and the bio-distribution of cells within time and the injection route. Results obtained showed that, after intramuscular administration of pre-labelled ECFCs, they remained around the injection zone. However, when the transplantation was intravenously, cells were translocated into other tissues. Therefore, ECFCs intramuscular administration promotes a more localized action in the injured area, as they remain distributed around the injection zone.