Elise Coffin, Alice Grangier, Guillaume Perrod, Max Piffoux, Iris Marangon, Imane Boucenna, Arthur Berger, Leila M’Harzi, Jessica Assouline, Thierry Lecomte, Anna Chipont, Coralie Guérin, Florence Gazeau, Claire Wilhelm, Christophe Cellier, Olivier Clément, Amanda Karine Andriola Silva, Gabriel Rahmi
Nanoscale, vol. 13, 2021 · DOI: 10.1039/d1nr01240a
Abstract
In our study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSC) contained in a thermoresponsive gel, Pluronic® F-127 (PF-127) to prevent stricture formation after endoscopic resection in a pig model. ADSC EVs were produced at the liter scale by a high-yield turbulence approach from ADSC 3D-cultured in bioreactors and characterized in terms of size, morphology and membrane markers. The thermoresponsive property of PF-127 gel was assessed by rheology. The pro-regenerative potency of ADSC EVs was investigated ex vivo in esophageal biopsies under starvation. In vivo tests were performed in a porcine model after extended esophageal endoscopic mucosal dissection (ESD). Pigs were randomized into 3 groups: control (n=6), gel (n=6) or combination of 1.45 × 1012 EVs + gel (n=6). Application of gel +/- EVs was performed just after ESD with a follow-up finalized at day 21 post ESD. There was a trend towards less feeding disorder in the EVs + gel group in comparison with the gel group and control one (16.67% vs. 66.7% vs. 83.33%, respectively), but without reaching a statistically significant difference. Significant decrease of the esophageal stricture rate was confirmed by endoscopic, radiological and histological examination for the EVs + gel group. A mean fibrosis area decrease and a larger regenerated muscularis mucosae were observed for the EVs + gel group. In summary, application of EVs + gel after extended esophageal endoscopic resection succeed to prevent stricture formation with an anti-fibrotic effect. This nano-therapy may be of interest to tackle a medical unmet need considering that esophageal stricture is the most challenging delayed complication after extended superficial cancer resection by endoscopy.