Thermoresponsive gel embedding extracellular vesicles from adipose stromal cells improves the healing of colonic anastomoses following irradiation in rats

嵌入脂肪基质细胞外囊泡的热敏凝胶可改善大鼠结肠吻合口照射后的愈合

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作者:Hadrien Alric #, Noëlle Mathieu #, Anna Sebbagh, Guillaume Peré, Christelle Demarquay, André Cronemberger, Arthur Berger, Benjamin Marcel, Claire Wilhelm, Florence Gazeau, Antoine Mariani, Mehdi Karoui, Olivier Clément, Irami Araujo-Filho, Amanda K A Silva #, Gabriel Rahmi #2

Abstract

Anastomotic leak occurrence is a severe complication after colorectal surgery. Considering the difficulty of treating these leaks and their impact on patient care, there is a strong need for an efficient prevention strategy. We evaluated a combination of extracellular vesicles (EVs) from rat adipose-derived stromal cells with a thermoresponsive gel, Pluronic® F127 (PF-127) to prevent anastomotic leaks. The pro-regenerative and immunomodulatory potencies of EVs are assessed in vitro. In vivo efficacy are assessed in rat with a colonic anastomosis model after irradiation. Endoscopic, anatomical and histological data show a consistent effect of EVs + gel on the healing of colonic anastomosis. These results are illustrated by a smaller anastomotic ulcer size, less fibrosis and less inflammatory infiltrations in the EVs + gel group. This multi-modal investigation is the first to point-out the translational potential of EVs combined with PF-127 for the healing of high-risk colorectal anastomosis.

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