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Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis

BACKGROUND: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats...

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Autores principales: Martín Arranz, Eduardo, Martín Arranz, María Dolores, Robredo, Tomás, Mancheño-Corvo, Pablo, Menta, Ramón, Alves, Francisco Javier, Suárez de Parga, Jose Manuel, Mora Sanz, Pedro, de la Rosa, Olga, Büscher, Dirk, Lombardo, Eleuterio, de Miguel, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892014/
https://www.ncbi.nlm.nih.gov/pubmed/29631607
http://dx.doi.org/10.1186/s13287-018-0837-x
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author Martín Arranz, Eduardo
Martín Arranz, María Dolores
Robredo, Tomás
Mancheño-Corvo, Pablo
Menta, Ramón
Alves, Francisco Javier
Suárez de Parga, Jose Manuel
Mora Sanz, Pedro
de la Rosa, Olga
Büscher, Dirk
Lombardo, Eleuterio
de Miguel, Fernando
author_facet Martín Arranz, Eduardo
Martín Arranz, María Dolores
Robredo, Tomás
Mancheño-Corvo, Pablo
Menta, Ramón
Alves, Francisco Javier
Suárez de Parga, Jose Manuel
Mora Sanz, Pedro
de la Rosa, Olga
Büscher, Dirk
Lombardo, Eleuterio
de Miguel, Fernando
author_sort Martín Arranz, Eduardo
collection PubMed
description BACKGROUND: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats. METHODS: Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (10(7) cells) or saline vehicle were endoscopically injected into the distal colon. Rats were followed for 11 days. Daily weight, endoscopic score at days 1 and 11, macroscopic appearance at necropsy, colon length and mRNA expression of Foxp3 and IL-10 in mesenteric lymph nodes (MLN) were analyzed. RESULTS: Endoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (− 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (− 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment. CONCLUSIONS: ASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-0837-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-58920142018-04-11 Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis Martín Arranz, Eduardo Martín Arranz, María Dolores Robredo, Tomás Mancheño-Corvo, Pablo Menta, Ramón Alves, Francisco Javier Suárez de Parga, Jose Manuel Mora Sanz, Pedro de la Rosa, Olga Büscher, Dirk Lombardo, Eleuterio de Miguel, Fernando Stem Cell Res Ther Research BACKGROUND: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats. METHODS: Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (10(7) cells) or saline vehicle were endoscopically injected into the distal colon. Rats were followed for 11 days. Daily weight, endoscopic score at days 1 and 11, macroscopic appearance at necropsy, colon length and mRNA expression of Foxp3 and IL-10 in mesenteric lymph nodes (MLN) were analyzed. RESULTS: Endoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (− 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (− 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment. CONCLUSIONS: ASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-0837-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-10 /pmc/articles/PMC5892014/ /pubmed/29631607 http://dx.doi.org/10.1186/s13287-018-0837-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Martín Arranz, Eduardo
Martín Arranz, María Dolores
Robredo, Tomás
Mancheño-Corvo, Pablo
Menta, Ramón
Alves, Francisco Javier
Suárez de Parga, Jose Manuel
Mora Sanz, Pedro
de la Rosa, Olga
Büscher, Dirk
Lombardo, Eleuterio
de Miguel, Fernando
Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis
title Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis
title_full Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis
title_fullStr Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis
title_full_unstemmed Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis
title_short Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis
title_sort endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates tnbs-induced colitis in rats and prevents stenosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892014/
https://www.ncbi.nlm.nih.gov/pubmed/29631607
http://dx.doi.org/10.1186/s13287-018-0837-x
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