Targeted cell replacement with bone marrow cells for airway epithelial regeneration
1 Latner Thoracic Surgery Research Laboratories, McEwen Centre for Regenerative Medicine, Toronto Lung Transplant Program, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto; and 2 Programme in Lung Biology, Hospital for Sick Children, Toronto, Ont...
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Veröffentlicht in: | American journal of physiology. Lung cellular and molecular physiology 2007-09, Vol.293 (3), p.L740-L752 |
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container_title | American journal of physiology. Lung cellular and molecular physiology |
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creator | Wong, Amy P Dutly, Andre E Sacher, Adrian Lee, Haeyul Hwang, David M Liu, Mingyao Keshavjee, Shaf Hu, Jim Waddell, Thomas K |
description | 1 Latner Thoracic Surgery Research Laboratories, McEwen Centre for Regenerative Medicine, Toronto Lung Transplant Program, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto; and 2 Programme in Lung Biology, Hospital for Sick Children, Toronto, Ontario, Canada
Submitted 2 February 2007
; accepted in final form 2 July 2007
It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.
bone marrow cell; lung; epithelium; airway regeneration
Address for reprint requests and other correspondence: T. K. Waddell, Toronto General Hospital, 9N-949, 200 Elizabeth St., Toronto, Ontario, Canada M5G 2C4 (e-mail: tom.waddell{at}uhn.on.ca ) |
doi_str_mv | 10.1152/ajplung.00050.2007 |
format | Article |
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Submitted 2 February 2007
; accepted in final form 2 July 2007
It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.
bone marrow cell; lung; epithelium; airway regeneration
Address for reprint requests and other correspondence: T. K. Waddell, Toronto General Hospital, 9N-949, 200 Elizabeth St., Toronto, Ontario, Canada M5G 2C4 (e-mail: tom.waddell{at}uhn.on.ca )</description><identifier>ISSN: 1040-0605</identifier><identifier>EISSN: 1522-1504</identifier><identifier>DOI: 10.1152/ajplung.00050.2007</identifier><identifier>PMID: 17616650</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Airway management ; Animals ; Biomarkers - metabolism ; Bone marrow ; Bone Marrow Cells - cytology ; Cell Differentiation ; Cell Fusion ; Cells ; Cells, Cultured ; Epithelial Cells - cytology ; Female ; Gene Expression Regulation ; Genotype & phenotype ; Green Fluorescent Proteins - metabolism ; Immunophenotyping ; Keratin-18 - metabolism ; Lungs ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Organ Specificity ; Promoter Regions, Genetic - genetics ; Regeneration ; Respiratory System - cytology ; Respiratory System - pathology ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Trachea - cytology ; Transgenes ; Uteroglobin - metabolism</subject><ispartof>American journal of physiology. Lung cellular and molecular physiology, 2007-09, Vol.293 (3), p.L740-L752</ispartof><rights>Copyright American Physiological Society Sep 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-7dd0190dafa058f44f6618b009c928d7741fe833001b677c9424804a78a91a9c3</citedby><cites>FETCH-LOGICAL-c416t-7dd0190dafa058f44f6618b009c928d7741fe833001b677c9424804a78a91a9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17616650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Amy P</creatorcontrib><creatorcontrib>Dutly, Andre E</creatorcontrib><creatorcontrib>Sacher, Adrian</creatorcontrib><creatorcontrib>Lee, Haeyul</creatorcontrib><creatorcontrib>Hwang, David M</creatorcontrib><creatorcontrib>Liu, Mingyao</creatorcontrib><creatorcontrib>Keshavjee, Shaf</creatorcontrib><creatorcontrib>Hu, Jim</creatorcontrib><creatorcontrib>Waddell, Thomas K</creatorcontrib><title>Targeted cell replacement with bone marrow cells for airway epithelial regeneration</title><title>American journal of physiology. Lung cellular and molecular physiology</title><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><description>1 Latner Thoracic Surgery Research Laboratories, McEwen Centre for Regenerative Medicine, Toronto Lung Transplant Program, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto; and 2 Programme in Lung Biology, Hospital for Sick Children, Toronto, Ontario, Canada
Submitted 2 February 2007
; accepted in final form 2 July 2007
It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.
bone marrow cell; lung; epithelium; airway regeneration
Address for reprint requests and other correspondence: T. K. Waddell, Toronto General Hospital, 9N-949, 200 Elizabeth St., Toronto, Ontario, Canada M5G 2C4 (e-mail: tom.waddell{at}uhn.on.ca )</description><subject>Airway management</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Cell Differentiation</subject><subject>Cell Fusion</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>Epithelial Cells - cytology</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Genotype & phenotype</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Immunophenotyping</subject><subject>Keratin-18 - metabolism</subject><subject>Lungs</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Organ Specificity</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Regeneration</subject><subject>Respiratory System - cytology</subject><subject>Respiratory System - pathology</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Trachea - cytology</subject><subject>Transgenes</subject><subject>Uteroglobin - metabolism</subject><issn>1040-0605</issn><issn>1522-1504</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1q3DAYRUVpadIkL9BFMV1058knWdbPsoSmLQx0kelaaOzPHg0ay5VsJvP21fyEQKErCXTO5eoS8pHCgtKa3dvt6OehXwBADQsGIN-Q6_zASloDf5vvwKEEAfUV-ZDS9sSBeE-uqBRUiBquydPKxh4nbIsGvS8ijt42uMNhKvZu2hTrMGCxszGG_YlIRRdiYV3c20OBY0bQO3sUexww2smF4Za866xPeHc5b8jvx2-rhx_l8tf3nw9fl2XDqZhK2bZANbS2s1CrjvNOCKrWALrRTLVSctqhqioAuhZSNpozroBbqaymVjfVDflyzh1j-DNjmszOpWNJO2CYkxGKUS6VyuDnf8BtmOOQuxlGQVMFdZUhdoaaGFKK2Jkxuvzzg6Fgjnuby97mtKM57p2lT5fkeb3D9lW5DJwBfQY2rt_sXUQzbg7JBR_6g3mcvV_h8_SSzHRlKrOUHMzYdtkt_---lHl1qr9avKHg</recordid><startdate>20070901</startdate><enddate>20070901</enddate><creator>Wong, Amy P</creator><creator>Dutly, Andre E</creator><creator>Sacher, Adrian</creator><creator>Lee, Haeyul</creator><creator>Hwang, David M</creator><creator>Liu, Mingyao</creator><creator>Keshavjee, Shaf</creator><creator>Hu, Jim</creator><creator>Waddell, Thomas K</creator><general>American Physiological Society</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>7QP</scope><scope>7TS</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20070901</creationdate><title>Targeted cell replacement with bone marrow cells for airway epithelial regeneration</title><author>Wong, Amy P ; Dutly, Andre E ; Sacher, Adrian ; Lee, Haeyul ; Hwang, David M ; Liu, Mingyao ; Keshavjee, Shaf ; Hu, Jim ; Waddell, Thomas K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-7dd0190dafa058f44f6618b009c928d7741fe833001b677c9424804a78a91a9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Airway management</topic><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - cytology</topic><topic>Cell Differentiation</topic><topic>Cell Fusion</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>Epithelial Cells - cytology</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Genotype & phenotype</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Immunophenotyping</topic><topic>Keratin-18 - metabolism</topic><topic>Lungs</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Organ Specificity</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Regeneration</topic><topic>Respiratory System - cytology</topic><topic>Respiratory System - pathology</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Trachea - cytology</topic><topic>Transgenes</topic><topic>Uteroglobin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Amy P</creatorcontrib><creatorcontrib>Dutly, Andre E</creatorcontrib><creatorcontrib>Sacher, Adrian</creatorcontrib><creatorcontrib>Lee, Haeyul</creatorcontrib><creatorcontrib>Hwang, David M</creatorcontrib><creatorcontrib>Liu, Mingyao</creatorcontrib><creatorcontrib>Keshavjee, Shaf</creatorcontrib><creatorcontrib>Hu, Jim</creatorcontrib><creatorcontrib>Waddell, Thomas K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Amy P</au><au>Dutly, Andre E</au><au>Sacher, Adrian</au><au>Lee, Haeyul</au><au>Hwang, David M</au><au>Liu, Mingyao</au><au>Keshavjee, Shaf</au><au>Hu, Jim</au><au>Waddell, Thomas K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted cell replacement with bone marrow cells for airway epithelial regeneration</atitle><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><date>2007-09-01</date><risdate>2007</risdate><volume>293</volume><issue>3</issue><spage>L740</spage><epage>L752</epage><pages>L740-L752</pages><issn>1040-0605</issn><eissn>1522-1504</eissn><abstract>1 Latner Thoracic Surgery Research Laboratories, McEwen Centre for Regenerative Medicine, Toronto Lung Transplant Program, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto; and 2 Programme in Lung Biology, Hospital for Sick Children, Toronto, Ontario, Canada
Submitted 2 February 2007
; accepted in final form 2 July 2007
It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.
bone marrow cell; lung; epithelium; airway regeneration
Address for reprint requests and other correspondence: T. K. Waddell, Toronto General Hospital, 9N-949, 200 Elizabeth St., Toronto, Ontario, Canada M5G 2C4 (e-mail: tom.waddell{at}uhn.on.ca )</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>17616650</pmid><doi>10.1152/ajplung.00050.2007</doi></addata></record> |
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source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
subjects | Airway management Animals Biomarkers - metabolism Bone marrow Bone Marrow Cells - cytology Cell Differentiation Cell Fusion Cells Cells, Cultured Epithelial Cells - cytology Female Gene Expression Regulation Genotype & phenotype Green Fluorescent Proteins - metabolism Immunophenotyping Keratin-18 - metabolism Lungs Male Mice Mice, Inbred C57BL Mice, Transgenic Organ Specificity Promoter Regions, Genetic - genetics Regeneration Respiratory System - cytology Respiratory System - pathology RNA, Messenger - genetics RNA, Messenger - metabolism Trachea - cytology Transgenes Uteroglobin - metabolism |
title | Targeted cell replacement with bone marrow cells for airway epithelial regeneration |
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