Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to-human model of xenotransplantation
Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate x...
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| Veröffentlicht in: | The Journal of thoracic and cardiovascular surgery 2000-04, Vol.119 (4), p.690-699 |
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| creator | Kulick, David M. Salerno, Christopher T. Dalmasso, Agustin P. Park, Soon J. Paz, Manuel Guzman Fodor, William L. Bolman, R.Morton |
| description | Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation.
Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation.
Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections.
Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a
P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L
–1 · min
–1, in contrast to the control group (1579 ± 722 mm Hg · L
–1 · min
–1;
P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm
–2 H
2O and 4.11 ± 2.84 mL · cm
–2 H
2O, respectively;
P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group.
Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation. (J Thorac Cardiovasc Surg 2000;119:690-9) |
| doi_str_mv | 10.1016/S0022-5223(00)70003-1 |
| format | Article |
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Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation.
Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections.
Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a
P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L
–1 · min
–1, in contrast to the control group (1579 ± 722 mm Hg · L
–1 · min
–1;
P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm
–2 H
2O and 4.11 ± 2.84 mL · cm
–2 H
2O, respectively;
P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group.
Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation. (J Thorac Cardiovasc Surg 2000;119:690-9)</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/S0022-5223(00)70003-1</identifier><identifier>PMID: 10733757</identifier><language>eng</language><publisher>United States: Mosby, Inc</publisher><subject>Animals ; CD59 Antigens - analysis ; Complement C3a - analysis ; Complement Hemolytic Activity Assay ; Fluorescent Antibody Technique ; Graft Survival - immunology ; Humans ; Immunoglobulin G - analysis ; Immunoglobulin M - analysis ; In Vitro Techniques ; Lung - immunology ; Lung - pathology ; Lung Compliance ; Lung Transplantation - immunology ; Pulmonary Circulation ; Swine ; Transplantation, Heterologous - immunology ; Vascular Resistance</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2000-04, Vol.119 (4), p.690-699</ispartof><rights>2000 Mosby, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-e94dac0653009159892772b62ac5a977bb625941f5f04f2041acb9e70d7dae923</citedby><cites>FETCH-LOGICAL-c440t-e94dac0653009159892772b62ac5a977bb625941f5f04f2041acb9e70d7dae923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0022-5223(00)70003-1$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10733757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kulick, David M.</creatorcontrib><creatorcontrib>Salerno, Christopher T.</creatorcontrib><creatorcontrib>Dalmasso, Agustin P.</creatorcontrib><creatorcontrib>Park, Soon J.</creatorcontrib><creatorcontrib>Paz, Manuel Guzman</creatorcontrib><creatorcontrib>Fodor, William L.</creatorcontrib><creatorcontrib>Bolman, R.Morton</creatorcontrib><title>Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to-human model of xenotransplantation</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation.
Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation.
Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections.
Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a
P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L
–1 · min
–1, in contrast to the control group (1579 ± 722 mm Hg · L
–1 · min
–1;
P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm
–2 H
2O and 4.11 ± 2.84 mL · cm
–2 H
2O, respectively;
P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group.
Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation. (J Thorac Cardiovasc Surg 2000;119:690-9)</description><subject>Animals</subject><subject>CD59 Antigens - analysis</subject><subject>Complement C3a - analysis</subject><subject>Complement Hemolytic Activity Assay</subject><subject>Fluorescent Antibody Technique</subject><subject>Graft Survival - immunology</subject><subject>Humans</subject><subject>Immunoglobulin G - analysis</subject><subject>Immunoglobulin M - analysis</subject><subject>In Vitro Techniques</subject><subject>Lung - immunology</subject><subject>Lung - pathology</subject><subject>Lung Compliance</subject><subject>Lung Transplantation - immunology</subject><subject>Pulmonary Circulation</subject><subject>Swine</subject><subject>Transplantation, Heterologous - immunology</subject><subject>Vascular Resistance</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu1DAQhi0EokvhEUA-UTgExk4cr08IVYUiVeJAkbhZXmeS9Sqxg-3Q9u3xNhXqjdPM4ftnfn2EvGbwgQFrP_4A4LwSnNfvAN5LAKgr9oRsGChZtVvx6ynZ_ENOyIuUDoWRwNRzcsJA1rUUckOW62h8GtA7S9ON80jHxQ-J4u0cMSXnB7pfJuOp7YSiJiKdY8hoM3a0j2Gizh-WeFcGNXR2Q5VDtQam0OFIQ09v0Yd8_DKPxmeTXfAvybPejAlfPcxT8vPLxfX5ZXX1_eu3889XlW0ayBWqpjMWWlEDKCbUVnEp-a7lxgqjpNyVVaiG9aKHpufQMGN3CiV0sjOoeH1K3q53S-nfC6asJ5csjqUIhiVpCUq1W2gLKFbQxpBSxF7P0U0m3mkG-uhb3_vWR5kaQN_71qzk3jw8WHYTdo9Sq-ACnK3A3g37GxdRp8mMY8GZPmSbGFO60a2CQn5aSSxC_jiMOlmH3mJXUjbrLrj_lPkLEvuePw</recordid><startdate>20000401</startdate><enddate>20000401</enddate><creator>Kulick, David M.</creator><creator>Salerno, Christopher T.</creator><creator>Dalmasso, Agustin P.</creator><creator>Park, Soon J.</creator><creator>Paz, Manuel Guzman</creator><creator>Fodor, William L.</creator><creator>Bolman, R.Morton</creator><general>Mosby, Inc</general><general>AATS/WTSA</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20000401</creationdate><title>Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to-human model of xenotransplantation</title><author>Kulick, David M. ; Salerno, Christopher T. ; Dalmasso, Agustin P. ; Park, Soon J. ; Paz, Manuel Guzman ; Fodor, William L. ; Bolman, R.Morton</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-e94dac0653009159892772b62ac5a977bb625941f5f04f2041acb9e70d7dae923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>CD59 Antigens - analysis</topic><topic>Complement C3a - analysis</topic><topic>Complement Hemolytic Activity Assay</topic><topic>Fluorescent Antibody Technique</topic><topic>Graft Survival - immunology</topic><topic>Humans</topic><topic>Immunoglobulin G - analysis</topic><topic>Immunoglobulin M - analysis</topic><topic>In Vitro Techniques</topic><topic>Lung - immunology</topic><topic>Lung - pathology</topic><topic>Lung Compliance</topic><topic>Lung Transplantation - immunology</topic><topic>Pulmonary Circulation</topic><topic>Swine</topic><topic>Transplantation, Heterologous - immunology</topic><topic>Vascular Resistance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kulick, David M.</creatorcontrib><creatorcontrib>Salerno, Christopher T.</creatorcontrib><creatorcontrib>Dalmasso, Agustin P.</creatorcontrib><creatorcontrib>Park, Soon J.</creatorcontrib><creatorcontrib>Paz, Manuel Guzman</creatorcontrib><creatorcontrib>Fodor, William L.</creatorcontrib><creatorcontrib>Bolman, R.Morton</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kulick, David M.</au><au>Salerno, Christopher T.</au><au>Dalmasso, Agustin P.</au><au>Park, Soon J.</au><au>Paz, Manuel Guzman</au><au>Fodor, William L.</au><au>Bolman, R.Morton</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to-human model of xenotransplantation</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2000-04-01</date><risdate>2000</risdate><volume>119</volume><issue>4</issue><spage>690</spage><epage>699</epage><pages>690-699</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><abstract>Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation.
Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation.
Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections.
Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a
P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L
–1 · min
–1, in contrast to the control group (1579 ± 722 mm Hg · L
–1 · min
–1;
P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm
–2 H
2O and 4.11 ± 2.84 mL · cm
–2 H
2O, respectively;
P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group.
Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation. (J Thorac Cardiovasc Surg 2000;119:690-9)</abstract><cop>United States</cop><pub>Mosby, Inc</pub><pmid>10733757</pmid><doi>10.1016/S0022-5223(00)70003-1</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals CD59 Antigens - analysis Complement C3a - analysis Complement Hemolytic Activity Assay Fluorescent Antibody Technique Graft Survival - immunology Humans Immunoglobulin G - analysis Immunoglobulin M - analysis In Vitro Techniques Lung - immunology Lung - pathology Lung Compliance Lung Transplantation - immunology Pulmonary Circulation Swine Transplantation, Heterologous - immunology Vascular Resistance |
| title | Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to-human model of xenotransplantation |
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