Extracellular vesicles from adipose stromal cells combined with athermoresponsive hydrogel prevent esophageal stricture afterextensive endoscopic submucosal dissection in a porcine model

  • Journal and date :

Nanoscale ; 2021

  • Authors :

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

  • Abstract :

In this study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSCs) and a thermoresponsive gel, Pluronic® F-127 (PF-127), to prevent stricture formation after endoscopic resection in a porcine model. ADSC EVs were produced at a liter scale by a high-yielding turbulence approach from ADSCs 3D cultured in bioreactors and characterized in terms of size, morphology and membrane markers. The thermoresponsive property of the 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 a combination of 1.45 × 1012 EVs + gel (n = 6). Application of gel ± EVs was performed just after ESD with a follow-up finalized on day 21 post-ESD. There was a trend towards less feeding disorder in the EV + gel group in comparison with the gel and the control groups (16.67% vs. 66.7% vs. 83.33%, respectively) but without reaching a statistically significant difference. A significant decrease in the esophageal stricture rate was confirmed by endoscopic, radiological and histological examination for the EV + gel group. A decrease in the mean fibrosis area and larger regenerated muscularis mucosae were observed for the EV + gel group. In summary, the application of EVs + gel after extended esophageal endoscopic resection succeeded in preventing stricture formation with an anti-fibrotic effect. This nano-therapy may be of interest to tackle an unmet medical need considering that esophageal stricture is the most challenging delayed complication after extended superficial cancer resection by endoscopy.

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