Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model
Clinical pig-to-human xenotransplantation might be associated with the risk of transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs). We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission fro...
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Veröffentlicht in: | Transplant international 2005-05, Vol.17 (12), p.848-858 |
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creator | WINKLER, Monica E WINKLER, Michael DENNER, Joachim MARTIN, Ulrich BURIAN, Rosemarie HECKER, Jens LOSS, Martin PRZEMECK, Michael LORENZ, Ralf PATIENCE, Clive KARLAS, Alexander SOMMER, Sebastian |
description | Clinical pig-to-human xenotransplantation might be associated with the risk of transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs). We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission from normal or transgenic porcine organs to human vascular tissue. Pig-to-human kidney xenotransplantation was performed in cynomolgus monkeys. An interposition graft constructed from a human saphena vein replaced the porcine kidney vein. After graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19 days), the human interposition grafts were removed. Human endothelial cells (huECs) were isolated from the interposition grafts and cultivated in vitro. Explanted human vascular tissue, isolated huECs, plasma and serum samples of the graft recipients were characterised by flow cytometry and immunohistochemistry and screened for indications of PERV transmission by quantitative polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assay. PERV-specific immune response of recipients was analysed by Western blot. No evidence of PERV infection or PERV-specific immune response was detected. |
doi_str_mv | 10.1007/s00147-005-0808-x |
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We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission from normal or transgenic porcine organs to human vascular tissue. Pig-to-human kidney xenotransplantation was performed in cynomolgus monkeys. An interposition graft constructed from a human saphena vein replaced the porcine kidney vein. After graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19 days), the human interposition grafts were removed. Human endothelial cells (huECs) were isolated from the interposition grafts and cultivated in vitro. Explanted human vascular tissue, isolated huECs, plasma and serum samples of the graft recipients were characterised by flow cytometry and immunohistochemistry and screened for indications of PERV transmission by quantitative polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assay. PERV-specific immune response of recipients was analysed by Western blot. No evidence of PERV infection or PERV-specific immune response was detected.</description><identifier>ISSN: 0934-0874</identifier><identifier>EISSN: 1432-2277</identifier><identifier>DOI: 10.1007/s00147-005-0808-x</identifier><identifier>PMID: 15864489</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing</publisher><subject>Animals ; Biological and medical sciences ; Cell Survival ; Cells, Cultured ; Endogenous Retroviruses ; Endothelial Cells - cytology ; Endothelial Cells - virology ; Flow Cytometry ; Graft Rejection - virology ; Graft Survival ; Humans ; Kidney Transplantation - adverse effects ; Macaca fascicularis ; Medical sciences ; Nephrology. Urinary tract diseases ; Pharmacology. Drug treatments ; Postoperative Complications - virology ; Swine ; Transplantation, Heterologous - adverse effects ; Zoonoses - transmission ; Zoonoses - virology</subject><ispartof>Transplant international, 2005-05, Vol.17 (12), p.848-858</ispartof><rights>2005 INIST-CNRS</rights><rights>Springer-Verlag 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-cf7048236c7c5e666ccea664b795b647e58951144a0bbd0b0f006bdb02a146f53</citedby><cites>FETCH-LOGICAL-c356t-cf7048236c7c5e666ccea664b795b647e58951144a0bbd0b0f006bdb02a146f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16896720$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15864489$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WINKLER, Monica E</creatorcontrib><creatorcontrib>WINKLER, Michael</creatorcontrib><creatorcontrib>DENNER, Joachim</creatorcontrib><creatorcontrib>MARTIN, Ulrich</creatorcontrib><creatorcontrib>BURIAN, Rosemarie</creatorcontrib><creatorcontrib>HECKER, Jens</creatorcontrib><creatorcontrib>LOSS, Martin</creatorcontrib><creatorcontrib>PRZEMECK, Michael</creatorcontrib><creatorcontrib>LORENZ, Ralf</creatorcontrib><creatorcontrib>PATIENCE, Clive</creatorcontrib><creatorcontrib>KARLAS, Alexander</creatorcontrib><creatorcontrib>SOMMER, Sebastian</creatorcontrib><title>Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model</title><title>Transplant international</title><addtitle>Transpl Int</addtitle><description>Clinical pig-to-human xenotransplantation might be associated with the risk of transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs). We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission from normal or transgenic porcine organs to human vascular tissue. Pig-to-human kidney xenotransplantation was performed in cynomolgus monkeys. An interposition graft constructed from a human saphena vein replaced the porcine kidney vein. After graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19 days), the human interposition grafts were removed. Human endothelial cells (huECs) were isolated from the interposition grafts and cultivated in vitro. Explanted human vascular tissue, isolated huECs, plasma and serum samples of the graft recipients were characterised by flow cytometry and immunohistochemistry and screened for indications of PERV transmission by quantitative polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assay. PERV-specific immune response of recipients was analysed by Western blot. No evidence of PERV infection or PERV-specific immune response was detected.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Endogenous Retroviruses</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - virology</subject><subject>Flow Cytometry</subject><subject>Graft Rejection - virology</subject><subject>Graft Survival</subject><subject>Humans</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Macaca fascicularis</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Pharmacology. Drug treatments</subject><subject>Postoperative Complications - virology</subject><subject>Swine</subject><subject>Transplantation, Heterologous - adverse effects</subject><subject>Zoonoses - transmission</subject><subject>Zoonoses - virology</subject><issn>0934-0874</issn><issn>1432-2277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhi0EotvCD-CCIiR6M4zjzxyrii-pEhc4W44zKS6JHeyk2v33eNmVKnGyZT_vaGYeQt4w-MAA9McCwISmAJKCAUP3z8iOCd7SttX6OdlBx0X90eKCXJbyAACtkfCSXDBplBCm25H9TXTToYTSpLFZwj1dE_21zS42S8o-RGwwDukeY9pKk3HN6THkel2zi2UOpYQUmxAbV1_CMiEtC_qApfkdhoiHZl-T_9hlcnF16xGf04DTK_JidFPB1-fzivz8_OnH7Vd69_3Lt9ubO-q5VCv1owZhWq689hKVUt6jU0r0upO9Ehql6SRjQjjo-wF6GAFUP_TQOibUKPkVuT7VXXL6s2FZbe3a41TbwTqTVUZwLvQRfPcf-JC2XLdTbMs6aYTkukLsBPmcSsk42iWH2eWDZWCPTuzJia1O7NGJ3dfM23PhrZ9xeEqcJVTg_RlwxbtprOvyoTxxynRKt8D_AvERlwM</recordid><startdate>200505</startdate><enddate>200505</enddate><creator>WINKLER, Monica E</creator><creator>WINKLER, Michael</creator><creator>DENNER, Joachim</creator><creator>MARTIN, Ulrich</creator><creator>BURIAN, Rosemarie</creator><creator>HECKER, Jens</creator><creator>LOSS, Martin</creator><creator>PRZEMECK, Michael</creator><creator>LORENZ, Ralf</creator><creator>PATIENCE, Clive</creator><creator>KARLAS, Alexander</creator><creator>SOMMER, Sebastian</creator><general>Blackwell Publishing</general><general>Blackwell Publishing Ltd</general><scope>IQODW</scope><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>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>200505</creationdate><title>Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model</title><author>WINKLER, Monica E ; WINKLER, Michael ; DENNER, Joachim ; MARTIN, Ulrich ; BURIAN, Rosemarie ; HECKER, Jens ; LOSS, Martin ; PRZEMECK, Michael ; LORENZ, Ralf ; PATIENCE, Clive ; KARLAS, Alexander ; SOMMER, Sebastian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-cf7048236c7c5e666ccea664b795b647e58951144a0bbd0b0f006bdb02a146f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>Endogenous Retroviruses</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - virology</topic><topic>Flow Cytometry</topic><topic>Graft Rejection - virology</topic><topic>Graft Survival</topic><topic>Humans</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Macaca fascicularis</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Pharmacology. Drug treatments</topic><topic>Postoperative Complications - virology</topic><topic>Swine</topic><topic>Transplantation, Heterologous - adverse effects</topic><topic>Zoonoses - transmission</topic><topic>Zoonoses - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WINKLER, Monica E</creatorcontrib><creatorcontrib>WINKLER, Michael</creatorcontrib><creatorcontrib>DENNER, Joachim</creatorcontrib><creatorcontrib>MARTIN, Ulrich</creatorcontrib><creatorcontrib>BURIAN, Rosemarie</creatorcontrib><creatorcontrib>HECKER, Jens</creatorcontrib><creatorcontrib>LOSS, Martin</creatorcontrib><creatorcontrib>PRZEMECK, Michael</creatorcontrib><creatorcontrib>LORENZ, Ralf</creatorcontrib><creatorcontrib>PATIENCE, Clive</creatorcontrib><creatorcontrib>KARLAS, Alexander</creatorcontrib><creatorcontrib>SOMMER, Sebastian</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplant international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WINKLER, Monica E</au><au>WINKLER, Michael</au><au>DENNER, Joachim</au><au>MARTIN, Ulrich</au><au>BURIAN, Rosemarie</au><au>HECKER, Jens</au><au>LOSS, Martin</au><au>PRZEMECK, Michael</au><au>LORENZ, Ralf</au><au>PATIENCE, Clive</au><au>KARLAS, Alexander</au><au>SOMMER, Sebastian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model</atitle><jtitle>Transplant international</jtitle><addtitle>Transpl Int</addtitle><date>2005-05</date><risdate>2005</risdate><volume>17</volume><issue>12</issue><spage>848</spage><epage>858</epage><pages>848-858</pages><issn>0934-0874</issn><eissn>1432-2277</eissn><abstract>Clinical pig-to-human xenotransplantation might be associated with the risk of transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs). We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission from normal or transgenic porcine organs to human vascular tissue. Pig-to-human kidney xenotransplantation was performed in cynomolgus monkeys. An interposition graft constructed from a human saphena vein replaced the porcine kidney vein. After graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19 days), the human interposition grafts were removed. Human endothelial cells (huECs) were isolated from the interposition grafts and cultivated in vitro. Explanted human vascular tissue, isolated huECs, plasma and serum samples of the graft recipients were characterised by flow cytometry and immunohistochemistry and screened for indications of PERV transmission by quantitative polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assay. PERV-specific immune response of recipients was analysed by Western blot. No evidence of PERV infection or PERV-specific immune response was detected.</abstract><cop>Oxford</cop><pub>Blackwell Publishing</pub><pmid>15864489</pmid><doi>10.1007/s00147-005-0808-x</doi><tpages>11</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Cell Survival Cells, Cultured Endogenous Retroviruses Endothelial Cells - cytology Endothelial Cells - virology Flow Cytometry Graft Rejection - virology Graft Survival Humans Kidney Transplantation - adverse effects Macaca fascicularis Medical sciences Nephrology. Urinary tract diseases Pharmacology. Drug treatments Postoperative Complications - virology Swine Transplantation, Heterologous - adverse effects Zoonoses - transmission Zoonoses - virology |
title | Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model |
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