A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics

Abstract Gastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, re...

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Autores principales:	Ling Li, Mohamad I. Itani, Kevan J. Salimian, Yue Li, Olaya Brewer Gutierrez, Haijie Hu, George Fayad, Jean A. Donet, Min Kyung Joo, Laura M. Ensign, Vivek Kumbhari, Florin M. Selaru
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0036aedcaedd4c609bd0bb02b3498583
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spelling	oai:doaj.org-article:0036aedcaedd4c609bd0bb02b34985832021-12-02T16:06:09ZA patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics10.1038/s41598-021-92628-82045-2322https://doaj.org/article/0036aedcaedd4c609bd0bb02b34985832021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92628-8https://doaj.org/toc/2045-2322Abstract Gastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.Ling LiMohamad I. ItaniKevan J. SalimianYue LiOlaya Brewer GutierrezHaijie HuGeorge FayadJean A. DonetMin Kyung JooLaura M. EnsignVivek KumbhariFlorin M. SelaruNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ling Li Mohamad I. Itani Kevan J. Salimian Yue Li Olaya Brewer Gutierrez Haijie Hu George Fayad Jean A. Donet Min Kyung Joo Laura M. Ensign Vivek Kumbhari Florin M. Selaru A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
description	Abstract Gastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.
format	article
author	Ling Li Mohamad I. Itani Kevan J. Salimian Yue Li Olaya Brewer Gutierrez Haijie Hu George Fayad Jean A. Donet Min Kyung Joo Laura M. Ensign Vivek Kumbhari Florin M. Selaru
author_facet	Ling Li Mohamad I. Itani Kevan J. Salimian Yue Li Olaya Brewer Gutierrez Haijie Hu George Fayad Jean A. Donet Min Kyung Joo Laura M. Ensign Vivek Kumbhari Florin M. Selaru
author_sort	Ling Li
title	A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
title_short	A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
title_full	A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
title_fullStr	A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
title_full_unstemmed	A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
title_sort	patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0036aedcaedd4c609bd0bb02b3498583
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A patient-like swine model of gastrointestinal fibrotic strictures for advancing therapeutics

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