Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease
Background: Delivery of genes encoding anti‐inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients...
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Veröffentlicht in: | Inflammatory bowel diseases 2005-05, Vol.11 (5), p.464-472 |
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description | Background: Delivery of genes encoding anti‐inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients with IBD compared with controls.
Methods: Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted β‐galactosidase reporter gene.
Results: X‐Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm2, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001).
Conclusions: We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible. |
doi_str_mv | 10.1097/01.MIB.0000158535.54428.a5 |
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Methods: Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted β‐galactosidase reporter gene.
Results: X‐Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm2, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001).
Conclusions: We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible.</description><identifier>ISSN: 1078-0998</identifier><identifier>EISSN: 1536-4844</identifier><identifier>DOI: 10.1097/01.MIB.0000158535.54428.a5</identifier><identifier>PMID: 15867586</identifier><language>eng</language><publisher>Philadelphia: Lippincott Williams & Wilkins, Inc</publisher><subject>Adenoviridae ; Adult ; beta-Galactosidase - genetics ; Biopsy ; Cell culture ; Colitis, Ulcerative - pathology ; Colon ; Colon - pathology ; Crohn Disease - pathology ; Crohn's disease ; Epithelial cells ; Epithelial Cells - physiology ; explant culture ; Explants ; Expression vectors ; Female ; gene therapy ; Genes, Reporter ; Genetic Vectors ; human ; Humans ; Inflammation ; inflammatory bowel disease ; Inflammatory bowel diseases ; Intestine ; Male ; Middle Aged ; Nuclei ; organ culture ; Reporter gene ; Tissue Culture Techniques ; Transduction, Genetic ; Ulcerative colitis</subject><ispartof>Inflammatory bowel diseases, 2005-05, Vol.11 (5), p.464-472</ispartof><rights>Copyright © 2005 Crohn's & Colitis Foundation of America, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3417-6d9be7244207603721028fdd725de096d79820ff479e981e3d5b8e994527b5ce3</citedby><cites>FETCH-LOGICAL-c3417-6d9be7244207603721028fdd725de096d79820ff479e981e3d5b8e994527b5ce3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1097%2F01.MIB.0000158535.54428.a5$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1097%2F01.MIB.0000158535.54428.a5$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15867586$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmiedlin‐Ren, Phyllissa</creatorcontrib><creatorcontrib>Kesisoglou, Filippos</creatorcontrib><creatorcontrib>Mapili, John A</creatorcontrib><creatorcontrib>Sabek, Sayed E</creatorcontrib><creatorcontrib>Barnett, Jeffrey L</creatorcontrib><creatorcontrib>Chey, William D</creatorcontrib><creatorcontrib>Roessler, Blake</creatorcontrib><creatorcontrib>Zimmermann, Ellen M</creatorcontrib><title>Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease</title><title>Inflammatory bowel diseases</title><addtitle>Inflamm Bowel Dis</addtitle><description>Background: Delivery of genes encoding anti‐inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients with IBD compared with controls.
Methods: Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted β‐galactosidase reporter gene.
Results: X‐Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm2, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001).
Conclusions: We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible.</description><subject>Adenoviridae</subject><subject>Adult</subject><subject>beta-Galactosidase - genetics</subject><subject>Biopsy</subject><subject>Cell culture</subject><subject>Colitis, Ulcerative - pathology</subject><subject>Colon</subject><subject>Colon - pathology</subject><subject>Crohn Disease - pathology</subject><subject>Crohn's disease</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - physiology</subject><subject>explant culture</subject><subject>Explants</subject><subject>Expression vectors</subject><subject>Female</subject><subject>gene therapy</subject><subject>Genes, Reporter</subject><subject>Genetic Vectors</subject><subject>human</subject><subject>Humans</subject><subject>Inflammation</subject><subject>inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Intestine</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nuclei</subject><subject>organ culture</subject><subject>Reporter gene</subject><subject>Tissue Culture Techniques</subject><subject>Transduction, Genetic</subject><subject>Ulcerative colitis</subject><issn>1078-0998</issn><issn>1536-4844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVUU1v3CAURFWrJk37FyrUQ3uy8wBjoLcmTZqVEuXSnhE2zwqVbbZgJ9p_X7a7Um6Ryod4oJk3jIaQTwxqBkadA6vvNhc1lMGklkLWsmm4rp18RU6ZFG3V6KZ5XWpQugJj9Al5l_NvAF6meUtOCq1VZZ-SuJn7hC6jp0tyc_Zrv4Q40zjQh3VyMw3zgnkJsxspbsPygGMoZY_jmGm3o87jHB9DKm-P2C8x5cIoaxjdNLly39EuPuFIfch7mffkzeDGjB-O5xn5dX318_Kmur3_sbn8dlv1omGqar3pUPFiC1QLQnEGXA_eKy49gmm9MprDMDTKoNEMhZedRmMayVUnexRn5Muh7zbFP2txYKeQ9792M8Y1WwNciJaBLMjPLyJbpbRQAgrw6wHYp5hzwsFuU5hc2lkGdh-MBWZLMPY5GPsvGOv2Kh-PKms3oX-mHpMogKsD4CmMuPuP1nZz8V0oDayYASX-AoR6nsI</recordid><startdate>200505</startdate><enddate>200505</enddate><creator>Schmiedlin‐Ren, Phyllissa</creator><creator>Kesisoglou, Filippos</creator><creator>Mapili, John A</creator><creator>Sabek, Sayed E</creator><creator>Barnett, Jeffrey L</creator><creator>Chey, William D</creator><creator>Roessler, Blake</creator><creator>Zimmermann, Ellen M</creator><general>Lippincott Williams & Wilkins, Inc</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><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>200505</creationdate><title>Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease</title><author>Schmiedlin‐Ren, Phyllissa ; Kesisoglou, Filippos ; Mapili, John A ; Sabek, Sayed E ; Barnett, Jeffrey L ; Chey, William D ; Roessler, Blake ; Zimmermann, Ellen M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3417-6d9be7244207603721028fdd725de096d79820ff479e981e3d5b8e994527b5ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenoviridae</topic><topic>Adult</topic><topic>beta-Galactosidase - genetics</topic><topic>Biopsy</topic><topic>Cell culture</topic><topic>Colitis, Ulcerative - pathology</topic><topic>Colon</topic><topic>Colon - pathology</topic><topic>Crohn Disease - pathology</topic><topic>Crohn's disease</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - physiology</topic><topic>explant culture</topic><topic>Explants</topic><topic>Expression vectors</topic><topic>Female</topic><topic>gene therapy</topic><topic>Genes, Reporter</topic><topic>Genetic Vectors</topic><topic>human</topic><topic>Humans</topic><topic>Inflammation</topic><topic>inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Intestine</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nuclei</topic><topic>organ culture</topic><topic>Reporter gene</topic><topic>Tissue Culture Techniques</topic><topic>Transduction, Genetic</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmiedlin‐Ren, Phyllissa</creatorcontrib><creatorcontrib>Kesisoglou, Filippos</creatorcontrib><creatorcontrib>Mapili, John A</creatorcontrib><creatorcontrib>Sabek, Sayed E</creatorcontrib><creatorcontrib>Barnett, Jeffrey L</creatorcontrib><creatorcontrib>Chey, William D</creatorcontrib><creatorcontrib>Roessler, Blake</creatorcontrib><creatorcontrib>Zimmermann, Ellen M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Inflammatory bowel diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmiedlin‐Ren, Phyllissa</au><au>Kesisoglou, Filippos</au><au>Mapili, John A</au><au>Sabek, Sayed E</au><au>Barnett, Jeffrey L</au><au>Chey, William D</au><au>Roessler, Blake</au><au>Zimmermann, Ellen M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease</atitle><jtitle>Inflammatory bowel diseases</jtitle><addtitle>Inflamm Bowel Dis</addtitle><date>2005-05</date><risdate>2005</risdate><volume>11</volume><issue>5</issue><spage>464</spage><epage>472</epage><pages>464-472</pages><issn>1078-0998</issn><eissn>1536-4844</eissn><abstract>Background: Delivery of genes encoding anti‐inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients with IBD compared with controls.
Methods: Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted β‐galactosidase reporter gene.
Results: X‐Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm2, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001).
Conclusions: We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible.</abstract><cop>Philadelphia</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>15867586</pmid><doi>10.1097/01.MIB.0000158535.54428.a5</doi><tpages>9</tpages></addata></record> |
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subjects | Adenoviridae Adult beta-Galactosidase - genetics Biopsy Cell culture Colitis, Ulcerative - pathology Colon Colon - pathology Crohn Disease - pathology Crohn's disease Epithelial cells Epithelial Cells - physiology explant culture Explants Expression vectors Female gene therapy Genes, Reporter Genetic Vectors human Humans Inflammation inflammatory bowel disease Inflammatory bowel diseases Intestine Male Middle Aged Nuclei organ culture Reporter gene Tissue Culture Techniques Transduction, Genetic Ulcerative colitis |
title | Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease |
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