Local administration of stem cell-derived extracellular vesicles in a thermoresponsive hydrogel promotes a pro-healing effect in a rat model of colo-cutaneous post-surgical fistula
Arthur Berger, Irami Araújo-Filho, Max Piffoux, Alba Nicolás‐Boluda, Alice Grangier, Imane Boucenna, Caroline Cristiano Real, Fábio Luiz Navarro Marques, Daniele de Paula Faria, Amália Cínthia Meneses do Rêgo, Chloé Broudin, Florence Gazeau, Claire Wilhelm, Olivier Clémеnt, Christophe Cellier, Carlos Alberto Buchpiguel, Gabriel Rahmi, Amanda Silva
Abstract
Zr was performed. Fistula external orifice and output assessment, probe-based confocal laser endomicroscopy, MRI and histology were carried out for therapy follow-up. The relevance of percutaneous EV administration embedded in the hydrogel vehicle was indicated by the PET-biodistribution study. Local administration of SC EVs in the hydrogel reduced colo-cutaneous fistula diameter, output, fibrosis and inflammation while increasing the density of neo-vessels when compared to the PBS and gel groups. This multi-modal investigation pointed-out the therapeutic potential of SC EVs administered locally and in a thermoresponsive hydrogel for the management of challenging post-surgical colon fistulas in a minimally-invasive cell-free strategy.