Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells
The tumorigenicity of human pluripotent stem cells is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a cell-surface-specific marker of human pluripotent stem cells that can be used to selectively remove Claudin-6-positi...
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| Veröffentlicht in: | Nature communications 2013-06, Vol.4 (1), p.1992-1992, Article 1992 |
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| creator | Ben-David, Uri Nudel, Neta Benvenisty, Nissim |
| description | The tumorigenicity of human pluripotent stem cells is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a cell-surface-specific marker of human pluripotent stem cells that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for human pluripotent stem cell survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed cell populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and
Clostridium perfringens
enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of human pluripotent stem cell-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated human pluripotent stem cells from culture, highlighting a strategy that may increase the safety of human pluripotent stem cell-based cell therapies.
The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David
et al.
identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures. |
| doi_str_mv | 10.1038/ncomms2992 |
| format | Article |
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Clostridium perfringens
enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of human pluripotent stem cell-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated human pluripotent stem cells from culture, highlighting a strategy that may increase the safety of human pluripotent stem cell-based cell therapies.
The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David
et al.
identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms2992</identifier><identifier>PMID: 23778593</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/1647/1407 ; 631/532/2064 ; 631/61/490 ; Animals ; Carcinogenesis - drug effects ; Carcinogenesis - metabolism ; Carcinogenesis - pathology ; Cell Death - drug effects ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Claudins - genetics ; Claudins - immunology ; Claudins - metabolism ; Down-Regulation - drug effects ; Down-Regulation - genetics ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; Embryonic Stem Cells - pathology ; Enterotoxins - pharmacology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Humanities and Social Sciences ; Humans ; Mice ; multidisciplinary ; Pluripotent Stem Cells - drug effects ; Pluripotent Stem Cells - metabolism ; Pluripotent Stem Cells - pathology ; Science ; Science (multidisciplinary) ; Teratoma - metabolism ; Teratoma - pathology ; Tight Junction Proteins - genetics ; Tight Junction Proteins - immunology ; Tight Junction Proteins - metabolism</subject><ispartof>Nature communications, 2013-06, Vol.4 (1), p.1992-1992, Article 1992</ispartof><rights>Springer Nature Limited 2013</rights><rights>Copyright Nature Publishing Group Jun 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-1b74ae5016d00ee9781cc10f61f039ec67b2b6063692aaeea27b12abfdbb9cdf3</citedby><cites>FETCH-LOGICAL-c453t-1b74ae5016d00ee9781cc10f61f039ec67b2b6063692aaeea27b12abfdbb9cdf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncomms2992$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://doi.org/10.1038/ncomms2992$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41096,42165,51551</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/ncomms2992$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23778593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ben-David, Uri</creatorcontrib><creatorcontrib>Nudel, Neta</creatorcontrib><creatorcontrib>Benvenisty, Nissim</creatorcontrib><title>Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>The tumorigenicity of human pluripotent stem cells is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a cell-surface-specific marker of human pluripotent stem cells that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for human pluripotent stem cell survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed cell populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and
Clostridium perfringens
enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of human pluripotent stem cell-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated human pluripotent stem cells from culture, highlighting a strategy that may increase the safety of human pluripotent stem cell-based cell therapies.
The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David
et al.
identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures.</description><subject>631/1647/1407</subject><subject>631/532/2064</subject><subject>631/61/490</subject><subject>Animals</subject><subject>Carcinogenesis - drug effects</subject><subject>Carcinogenesis - metabolism</subject><subject>Carcinogenesis - pathology</subject><subject>Cell Death - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Claudins - genetics</subject><subject>Claudins - immunology</subject><subject>Claudins - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Down-Regulation - genetics</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Embryonic Stem Cells - 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Academic</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Ben-David, Uri</au><au>Nudel, Neta</au><au>Benvenisty, Nissim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2013-06-18</date><risdate>2013</risdate><volume>4</volume><issue>1</issue><spage>1992</spage><epage>1992</epage><pages>1992-1992</pages><artnum>1992</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>The tumorigenicity of human pluripotent stem cells is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a cell-surface-specific marker of human pluripotent stem cells that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for human pluripotent stem cell survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed cell populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and
Clostridium perfringens
enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of human pluripotent stem cell-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated human pluripotent stem cells from culture, highlighting a strategy that may increase the safety of human pluripotent stem cell-based cell therapies.
The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David
et al.
identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23778593</pmid><doi>10.1038/ncomms2992</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature OA Free Journals |
| subjects | 631/1647/1407 631/532/2064 631/61/490 Animals Carcinogenesis - drug effects Carcinogenesis - metabolism Carcinogenesis - pathology Cell Death - drug effects Cell Differentiation - drug effects Cell Proliferation - drug effects Cell Survival - drug effects Claudins - genetics Claudins - immunology Claudins - metabolism Down-Regulation - drug effects Down-Regulation - genetics Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism Embryonic Stem Cells - pathology Enterotoxins - pharmacology Fibroblasts - drug effects Fibroblasts - metabolism Fibroblasts - pathology Humanities and Social Sciences Humans Mice multidisciplinary Pluripotent Stem Cells - drug effects Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - pathology Science Science (multidisciplinary) Teratoma - metabolism Teratoma - pathology Tight Junction Proteins - genetics Tight Junction Proteins - immunology Tight Junction Proteins - metabolism |
| title | Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells |
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