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P045 Local administration of extracellular vesicles from adipose-derived stromal cells promote healing in a rat model of radiation colitis – a pilot study

Title: P045 Local administration of extracellular vesicles from adipose-derived stromal cells promote healing in a rat model of radiation colitis – a pilot study
Authors: Sebbagh, A; Mathieu, N; Demarquay, C; Geiger, M; Sémont, A; Simon, C; Branchu, J; Milliat, F; Gazeau, F; Wilhelm, C; Silva Brun, A; Rahmi, G
Source: Journal of Crohn's and Colitis ; volume 17, issue Supplement_1, page i212-i213 ; ISSN 1873-9946 1876-4479
Publisher Information: Oxford University Press (OUP)
Publication Year: 2023
Description: Background The estimated increase in prevalence of radiation enteropathy associated with a current scarcity of effective treatment options underline the need for the development of new therapies. Extracellular vesicles (EV), which are membrane-bound particles secreted by cells containing proteins, lipids and nucleic acids, have yielded promising preclinical results in various applications in regenerative medicine. Here, we aimed to investigate whether EV from adipose-derived stromal cells (ADSC) may present a therapeutic potential in the context of radiation colitis. Methods EV were produced from primary rat ADSC by exposure to a turbulent flow. Radiation colitis was induced by fractionated irradiation at a dose of 3x10Gy on a colorectal window (3x2cm) in male Sprague-Dawley rats (311-386g) at days 0, 2 and 4; following a pre-established protocol. Treatment was administered at days 11 and 15 through submucosal endoscopic injections of rat ADSC (n=9 rats, 2x106cells per dose), EV (n=9 rats, 1.06x1011 particles per dose), or an equivalent volume of saline (n=10 rats). The rats were sacrificed at day 17. Our primary endpoint was the extent of colonic epithelial injury at histological analysis (Table 1). Secondary endpoints included an endoscopic assessment of the severity of lesions at day 15 (Table 2) and an evaluation of macrophage infiltration in the colonic mucosa by CD68 immunohistochemistry. Comparisons of proportions were performed by the Chi-squared test followed by Fisher’s exact test. Results In the ADSC group, 1 rat died from anaesthesia complications. No other adverse effects were observed. No differences in total body weight evolution were observed between the groups. At day 15, a statistically significant decrease of the proportion of animals with moderate to severe lesions was evidenced by endoscopy in the EV group compared to the saline group (p=0.0031; Figure 1). No differences were observed between the other groups. Histological analysis of the colonic epithelial injury score evidenced a ...
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/ecco-jcc/jjac190.0175
Availability: https://doi.org/10.1093/ecco-jcc/jjac190.0175; https://academic.oup.com/ecco-jcc/article-pdf/17/Supplement_1/i212/51509532/jjac190.0175.pdf
Rights: https://academic.oup.com/pages/standard-publication-reuse-rights
Accession Number: edsbas.6A12C19B
Database: BASE