Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis

Abstract Background The current methodologies for the identification of therapeutic targets for inflammatory bowel disease (IBD) are limited to conventional 2-dimensional (2D) cell cultures and animal models. The use of 3D decellularized human intestinal scaffolds obtained from surgically resected i...

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Veröffentlicht in:Inflammatory bowel diseases 2019-10, Vol.25 (11), p.1740-1750
Hauptverfasser: Giuffrida, Paolo, Curti, Marco, Al-Akkad, Walid, Biel, Carin, Crowley, Claire, Frenguelli, Luca, Telese, Andrea, Hall, Andrew, Tamburrino, Domenico, Spoletini, Gabriele, Fusai, Giuseppe, Tinozzi, Francesco Paolo, Pietrabissa, Andrea, Corazza, Gino Roberto, De Coppi, Paolo, Pinzani, Massimo, Di Sabatino, Antonio, Rombouts, Krista, Mazza, Giuseppe
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container_end_page 1750
container_issue 11
container_start_page 1740
container_title Inflammatory bowel diseases
container_volume 25
creator Giuffrida, Paolo
Curti, Marco
Al-Akkad, Walid
Biel, Carin
Crowley, Claire
Frenguelli, Luca
Telese, Andrea
Hall, Andrew
Tamburrino, Domenico
Spoletini, Gabriele
Fusai, Giuseppe
Tinozzi, Francesco Paolo
Pietrabissa, Andrea
Corazza, Gino Roberto
De Coppi, Paolo
Pinzani, Massimo
Di Sabatino, Antonio
Rombouts, Krista
Mazza, Giuseppe
description Abstract Background The current methodologies for the identification of therapeutic targets for inflammatory bowel disease (IBD) are limited to conventional 2-dimensional (2D) cell cultures and animal models. The use of 3D decellularized human intestinal scaffolds obtained from surgically resected intestine and engineered with human intestinal cells may provide a major advancement in the development of innovative intestinal disease models. The aim of the present study was to design and validate a decellularization protocol for the production of acellular 3D extracellular matrix (ECM) scaffolds from the human duodenum. Methods Scaffolds were characterized by verifying the preservation of the ECM protein composition and 3D architecture of the native intestine and were employed for tissue engineering with primary human intestinal myofibroblasts for up to 14 days. Results Engrafted cells showed the ability to grow and remodel the surrounding ECM. mRNA expression of key genes involved in ECM turnover was significantly different when comparing primary human intestinal myofibroblasts cultured in 3D scaffolds with those cultured in standard 2D cultures on plastic dishes. Moreover, incubation with key profibrogenic growth factors such as TGFβ1 and PDGF-BB resulted in markedly different effects in standard 2D vs 3D cultures, further emphasizing the importance of using 3D cell cultures. Conclusions These results confirm the feasibility of 3D culture of human intestinal myofibroblasts in intestinal ECM scaffolds as an innovative platform for disease modeling, biomarker discovery, and drug testing in intestinal fibrosis. We successfully developed a novel and reproducible protocol designed to “decellularize-recellularize” acellular 3D extracellular matrix (ECM) scaffolds from human intestine. 3D cultures of intestinal myofibroblasts in ECM scaffolds represent a key alterative to 2D cultures on plastic and animal models.
doi_str_mv 10.1093/ibd/izz115
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The use of 3D decellularized human intestinal scaffolds obtained from surgically resected intestine and engineered with human intestinal cells may provide a major advancement in the development of innovative intestinal disease models. The aim of the present study was to design and validate a decellularization protocol for the production of acellular 3D extracellular matrix (ECM) scaffolds from the human duodenum. Methods Scaffolds were characterized by verifying the preservation of the ECM protein composition and 3D architecture of the native intestine and were employed for tissue engineering with primary human intestinal myofibroblasts for up to 14 days. Results Engrafted cells showed the ability to grow and remodel the surrounding ECM. mRNA expression of key genes involved in ECM turnover was significantly different when comparing primary human intestinal myofibroblasts cultured in 3D scaffolds with those cultured in standard 2D cultures on plastic dishes. Moreover, incubation with key profibrogenic growth factors such as TGFβ1 and PDGF-BB resulted in markedly different effects in standard 2D vs 3D cultures, further emphasizing the importance of using 3D cell cultures. Conclusions These results confirm the feasibility of 3D culture of human intestinal myofibroblasts in intestinal ECM scaffolds as an innovative platform for disease modeling, biomarker discovery, and drug testing in intestinal fibrosis. We successfully developed a novel and reproducible protocol designed to “decellularize-recellularize” acellular 3D extracellular matrix (ECM) scaffolds from human intestine. 3D cultures of intestinal myofibroblasts in ECM scaffolds represent a key alterative to 2D cultures on plastic and animal models.</description><identifier>ISSN: 1078-0998</identifier><identifier>EISSN: 1536-4844</identifier><identifier>DOI: 10.1093/ibd/izz115</identifier><identifier>PMID: 31199863</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Cell Culture Techniques - methods ; Cells, Cultured ; Duodenum - pathology ; Duodenum - ultrastructure ; Extracellular Matrix - chemistry ; Fibrosis ; Gastrointestinal diseases ; Health aspects ; Humans ; Microscopy, Electron ; Platelet-derived growth factor ; RNA ; Tissue Engineering ; Tissue Scaffolds - chemistry ; Transforming growth factors</subject><ispartof>Inflammatory bowel diseases, 2019-10, Vol.25 (11), p.1740-1750</ispartof><rights>2019 Crohn’s &amp; Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2019</rights><rights>2019 Crohn’s &amp; Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-2112546f2f030ef0a771b5ca373e8a8dec8c8d506a739d654cd72681e90b11453</citedby><cites>FETCH-LOGICAL-c420t-2112546f2f030ef0a771b5ca373e8a8dec8c8d506a739d654cd72681e90b11453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31199863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giuffrida, Paolo</creatorcontrib><creatorcontrib>Curti, Marco</creatorcontrib><creatorcontrib>Al-Akkad, Walid</creatorcontrib><creatorcontrib>Biel, Carin</creatorcontrib><creatorcontrib>Crowley, Claire</creatorcontrib><creatorcontrib>Frenguelli, Luca</creatorcontrib><creatorcontrib>Telese, Andrea</creatorcontrib><creatorcontrib>Hall, Andrew</creatorcontrib><creatorcontrib>Tamburrino, Domenico</creatorcontrib><creatorcontrib>Spoletini, Gabriele</creatorcontrib><creatorcontrib>Fusai, Giuseppe</creatorcontrib><creatorcontrib>Tinozzi, Francesco Paolo</creatorcontrib><creatorcontrib>Pietrabissa, Andrea</creatorcontrib><creatorcontrib>Corazza, Gino Roberto</creatorcontrib><creatorcontrib>De Coppi, Paolo</creatorcontrib><creatorcontrib>Pinzani, Massimo</creatorcontrib><creatorcontrib>Di Sabatino, Antonio</creatorcontrib><creatorcontrib>Rombouts, Krista</creatorcontrib><creatorcontrib>Mazza, Giuseppe</creatorcontrib><title>Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis</title><title>Inflammatory bowel diseases</title><addtitle>Inflamm Bowel Dis</addtitle><description>Abstract Background The current methodologies for the identification of therapeutic targets for inflammatory bowel disease (IBD) are limited to conventional 2-dimensional (2D) cell cultures and animal models. The use of 3D decellularized human intestinal scaffolds obtained from surgically resected intestine and engineered with human intestinal cells may provide a major advancement in the development of innovative intestinal disease models. The aim of the present study was to design and validate a decellularization protocol for the production of acellular 3D extracellular matrix (ECM) scaffolds from the human duodenum. Methods Scaffolds were characterized by verifying the preservation of the ECM protein composition and 3D architecture of the native intestine and were employed for tissue engineering with primary human intestinal myofibroblasts for up to 14 days. Results Engrafted cells showed the ability to grow and remodel the surrounding ECM. mRNA expression of key genes involved in ECM turnover was significantly different when comparing primary human intestinal myofibroblasts cultured in 3D scaffolds with those cultured in standard 2D cultures on plastic dishes. Moreover, incubation with key profibrogenic growth factors such as TGFβ1 and PDGF-BB resulted in markedly different effects in standard 2D vs 3D cultures, further emphasizing the importance of using 3D cell cultures. Conclusions These results confirm the feasibility of 3D culture of human intestinal myofibroblasts in intestinal ECM scaffolds as an innovative platform for disease modeling, biomarker discovery, and drug testing in intestinal fibrosis. We successfully developed a novel and reproducible protocol designed to “decellularize-recellularize” acellular 3D extracellular matrix (ECM) scaffolds from human intestine. 3D cultures of intestinal myofibroblasts in ECM scaffolds represent a key alterative to 2D cultures on plastic and animal models.</description><subject>Cell Culture Techniques - methods</subject><subject>Cells, Cultured</subject><subject>Duodenum - pathology</subject><subject>Duodenum - ultrastructure</subject><subject>Extracellular Matrix - chemistry</subject><subject>Fibrosis</subject><subject>Gastrointestinal diseases</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Microscopy, Electron</subject><subject>Platelet-derived growth factor</subject><subject>RNA</subject><subject>Tissue Engineering</subject><subject>Tissue Scaffolds - chemistry</subject><subject>Transforming growth factors</subject><issn>1078-0998</issn><issn>1536-4844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1L5TAQhsOy4td6sz9AAosgQjXTtE16efAbRBfR6zBNp2ukH8ekvfD8enOoLggiAzPD8MzLDC9jv0EcgyjliavqE7daAeQ_2DbkskgynWU_Yy-UTkRZ6i22E8KzEGmMcpNtSYA4LeQ2ezwjS207tejdimp-NXXY88tp5Bg48lscJ48tl2f8b4tjM_iOx8TvKRB6-8Rdz6_7kcLo-ohduMoPwYVfbKPBNtDee91ljxfnD6dXyc3d5fXp4iaxWSrGJAVI86xo0kZIQY1ApaDKLUolSaOuyWqr61wUqGRZF3lma5UWGqgUFUCWy112OOsu_fAyxStM58L6H-xpmIJJpVAgoVQqon9m9B-2ZFzfDKNHu8bNogAtZKrlmjr-gopRU-fs0FPj4vzTwtG8YOPjwVNjlt516F8NCLN2x0R3zOxOhPffz52qjur_6IcdETiYgWFafif0BiJ3lTc</recordid><startdate>20191018</startdate><enddate>20191018</enddate><creator>Giuffrida, Paolo</creator><creator>Curti, Marco</creator><creator>Al-Akkad, Walid</creator><creator>Biel, Carin</creator><creator>Crowley, Claire</creator><creator>Frenguelli, Luca</creator><creator>Telese, Andrea</creator><creator>Hall, Andrew</creator><creator>Tamburrino, Domenico</creator><creator>Spoletini, Gabriele</creator><creator>Fusai, Giuseppe</creator><creator>Tinozzi, Francesco Paolo</creator><creator>Pietrabissa, Andrea</creator><creator>Corazza, Gino Roberto</creator><creator>De Coppi, Paolo</creator><creator>Pinzani, Massimo</creator><creator>Di Sabatino, Antonio</creator><creator>Rombouts, Krista</creator><creator>Mazza, Giuseppe</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20191018</creationdate><title>Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis</title><author>Giuffrida, Paolo ; 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The use of 3D decellularized human intestinal scaffolds obtained from surgically resected intestine and engineered with human intestinal cells may provide a major advancement in the development of innovative intestinal disease models. The aim of the present study was to design and validate a decellularization protocol for the production of acellular 3D extracellular matrix (ECM) scaffolds from the human duodenum. Methods Scaffolds were characterized by verifying the preservation of the ECM protein composition and 3D architecture of the native intestine and were employed for tissue engineering with primary human intestinal myofibroblasts for up to 14 days. Results Engrafted cells showed the ability to grow and remodel the surrounding ECM. mRNA expression of key genes involved in ECM turnover was significantly different when comparing primary human intestinal myofibroblasts cultured in 3D scaffolds with those cultured in standard 2D cultures on plastic dishes. Moreover, incubation with key profibrogenic growth factors such as TGFβ1 and PDGF-BB resulted in markedly different effects in standard 2D vs 3D cultures, further emphasizing the importance of using 3D cell cultures. Conclusions These results confirm the feasibility of 3D culture of human intestinal myofibroblasts in intestinal ECM scaffolds as an innovative platform for disease modeling, biomarker discovery, and drug testing in intestinal fibrosis. We successfully developed a novel and reproducible protocol designed to “decellularize-recellularize” acellular 3D extracellular matrix (ECM) scaffolds from human intestine. 3D cultures of intestinal myofibroblasts in ECM scaffolds represent a key alterative to 2D cultures on plastic and animal models.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>31199863</pmid><doi>10.1093/ibd/izz115</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Cell Culture Techniques - methods
Cells, Cultured
Duodenum - pathology
Duodenum - ultrastructure
Extracellular Matrix - chemistry
Fibrosis
Gastrointestinal diseases
Health aspects
Humans
Microscopy, Electron
Platelet-derived growth factor
RNA
Tissue Engineering
Tissue Scaffolds - chemistry
Transforming growth factors
title Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis
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