Xenotransplantation of Galactosyl-Transferase Knockout, CD55, CD59, CD39, and Fucosyl-Transferase Transgenic Pig Kidneys Into Baboons
Identifieur interne : 006547 ( Main/Curation ); précédent : 006546; suivant : 006548Xenotransplantation of Galactosyl-Transferase Knockout, CD55, CD59, CD39, and Fucosyl-Transferase Transgenic Pig Kidneys Into Baboons
Auteurs : S. Le Bas-Bernardet [France] ; X. Tillou [France] ; N. Poirier [France] ; N. Dilek [France] ; M. Chatelais [France] ; J. Devalliere [France] ; B. Charreau [France] ; D. Minault [France] ; J. Hervouet [France] ; K. Renaudin [France] ; C. Crossan [Royaume-Uni] ; L. Scobie [Royaume-Uni] ; P. J. Cowan [Australie] ; A. J. F. D'Apice [Australie] ; C. Galli [Italie] ; E. Cozzi [Italie] ; J. P. Soulillou [France] ; B. Vanhove [France] ; G. Blancho [France]Source :
- Transplantation proceedings [ 0041-1345 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Animal transgénique, Singe, Médecine.
English descriptors
- KwdEn :
Abstract
Galactosyl-transferase knockout (GT-KO) pigs represent the latest major progress to reduce immune reactions in xenotransplantation. However, their organs are still subject to rapid humoral rejection involving complement activation requiring the ongoing development of further genetic modifications in the pig. In a pig-to-baboon renal transplantation setting, we have used donor pigs that are not only GT-KO, but also transgenic for human CD55 (hCD55), hCD59, hCD39, and fucosyl-transferase (hHT). We studied kidney xenograft survival, physiological and immunologic parameters, xenogeneic rejection characteristics, as well as viral transmission aspects among two groups of baboons: control animals (n = 2), versus those (n = 4) treated with a cocktail of cyclophosphamide, tacrolimus, mycophenolate mofetil, steroids, and a recombinant human C1 inhibitor. Whereas control animals showed clear acute humoral rejection at around day 4, the treated animals showed moderately improved graft survival with rejection at around 2 weeks posttransplantation. Biopsies showed signs of acute vascular rejection (interstitial hemorrhage, glomerular thrombi, and acute tubular necrosis) as well as immunoglobulin (Ig)M and complement deposition in the glomerular and peritubular capillaries. The low level of preformed non-Gal-α1.3Gal IgM detected prior to transplantation increased at 6 days posttransplantation, whereas induced IgG appeared after day 6. No porcine endogenous retrovirus (PERV) transmission was detected in any transplanted baboon. Thus, surprisingly, organs from the GT-KO, hCD55, hCD59, hCD39, and hHT transgenic donors did not appear to convey significant protection against baboon anti-pig antibodies and complement activation, which obviously continue to be significant factors under a suboptimal immunosuppression regimen. The association, timing, and doses of immunosuppressive drugs remain critical. They will have to be optimized to achieve longer graft survivals.
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001737
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Links to Exploration step
Pascal:12-0017503Le document en format XML
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<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dilek, N" sort="Dilek, N" uniqKey="Dilek N" first="N." last="Dilek">N. Dilek</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chatelais, M" sort="Chatelais, M" uniqKey="Chatelais M" first="M." last="Chatelais">M. Chatelais</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Devalliere, J" sort="Devalliere, J" uniqKey="Devalliere J" first="J." last="Devalliere">J. Devalliere</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Charreau, B" sort="Charreau, B" uniqKey="Charreau B" first="B." last="Charreau">B. Charreau</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Minault, D" sort="Minault, D" uniqKey="Minault D" first="D." last="Minault">D. Minault</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hervouet, J" sort="Hervouet, J" uniqKey="Hervouet J" first="J." last="Hervouet">J. Hervouet</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Renaudin, K" sort="Renaudin, K" uniqKey="Renaudin K" first="K." last="Renaudin">K. Renaudin</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Pathology Laboratory, CHU-Hôtel Dieu</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Crossan, C" sort="Crossan, C" uniqKey="Crossan C" first="C." last="Crossan">C. Crossan</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1>
<s2>Glasgow</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Glasgow</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Scobie, L" sort="Scobie, L" uniqKey="Scobie L" first="L." last="Scobie">L. Scobie</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1>
<s2>Glasgow</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Glasgow</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cowan, P J" sort="Cowan, P J" uniqKey="Cowan P" first="P. J." last="Cowan">P. J. Cowan</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="D Apice, A J F" sort="D Apice, A J F" uniqKey="D Apice A" first="A. J. F." last="D'Apice">A. J. F. D'Apice</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Galli, C" sort="Galli, C" uniqKey="Galli C" first="C." last="Galli">C. Galli</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>The Laboratorio di Tecnologie della Riproduzione, LTR</s1>
<s2>Cremona</s2>
<s3>ITA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Italie</country>
<wicri:noRegion>Cremona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cozzi, E" sort="Cozzi, E" uniqKey="Cozzi E" first="E." last="Cozzi">E. Cozzi</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Consorzio per la Ricerca sul Trapianto d'Organi, CORIT</s1>
<s2>Padua</s2>
<s3>ITA</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Italie</country>
<wicri:noRegion>Padua</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Soulillou, J P" sort="Soulillou, J P" uniqKey="Soulillou J" first="J. P." last="Soulillou">J. P. Soulillou</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vanhove, B" sort="Vanhove, B" uniqKey="Vanhove B" first="B." last="Vanhove">B. Vanhove</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Blancho, G" sort="Blancho, G" uniqKey="Blancho G" first="G." last="Blancho">G. Blancho</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Transplantation proceedings</title>
<title level="j" type="abbreviated">Transplant. proc.</title>
<idno type="ISSN">0041-1345</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Transplantation proceedings</title>
<title level="j" type="abbreviated">Transplant. proc.</title>
<idno type="ISSN">0041-1345</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Baboon</term>
<term>Decay accelerating factor</term>
<term>Gene</term>
<term>Graft</term>
<term>Heterotransplantation</term>
<term>Kidney</term>
<term>Medicine</term>
<term>Monkey</term>
<term>Mutation</term>
<term>Pig</term>
<term>Primates</term>
<term>Transferases</term>
<term>Transgenic animal</term>
<term>Transplantation</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Hétérotransplantation</term>
<term>Transferases</term>
<term>Gène</term>
<term>Mutation</term>
<term>Facteur accélérateur dissociation</term>
<term>Animal transgénique</term>
<term>Porc</term>
<term>Rein</term>
<term>Primates</term>
<term>Singe</term>
<term>Médecine</term>
<term>Transplantation</term>
<term>Greffe</term>
<term>Traitement</term>
<term>Antigène CD55</term>
<term>Antigène CD59</term>
<term>Antigène CD39</term>
<term>Babouin</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Animal transgénique</term>
<term>Singe</term>
<term>Médecine</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Galactosyl-transferase knockout (GT-KO) pigs represent the latest major progress to reduce immune reactions in xenotransplantation. However, their organs are still subject to rapid humoral rejection involving complement activation requiring the ongoing development of further genetic modifications in the pig. In a pig-to-baboon renal transplantation setting, we have used donor pigs that are not only GT-KO, but also transgenic for human CD55 (hCD55), hCD59, hCD39, and fucosyl-transferase (hHT). We studied kidney xenograft survival, physiological and immunologic parameters, xenogeneic rejection characteristics, as well as viral transmission aspects among two groups of baboons: control animals (n = 2), versus those (n = 4) treated with a cocktail of cyclophosphamide, tacrolimus, mycophenolate mofetil, steroids, and a recombinant human C1 inhibitor. Whereas control animals showed clear acute humoral rejection at around day 4, the treated animals showed moderately improved graft survival with rejection at around 2 weeks posttransplantation. Biopsies showed signs of acute vascular rejection (interstitial hemorrhage, glomerular thrombi, and acute tubular necrosis) as well as immunoglobulin (Ig)M and complement deposition in the glomerular and peritubular capillaries. The low level of preformed non-Gal-α1.3Gal IgM detected prior to transplantation increased at 6 days posttransplantation, whereas induced IgG appeared after day 6. No porcine endogenous retrovirus (PERV) transmission was detected in any transplanted baboon. Thus, surprisingly, organs from the GT-KO, hCD55, hCD59, hCD39, and hHT transgenic donors did not appear to convey significant protection against baboon anti-pig antibodies and complement activation, which obviously continue to be significant factors under a suboptimal immunosuppression regimen. The association, timing, and doses of immunosuppressive drugs remain critical. They will have to be optimized to achieve longer graft survivals.</div>
</front>
</TEI>
</record>
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