Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response
Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Butler, James R. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2016transfer abstract |
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| Umfang: |
5 |
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| Übergeordnetes Werk: |
Enthalten in: Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing - Quinlan-Colwell, Ann ELSEVIER, 2021, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:35 ; year:2016 ; pages:47-51 ; extent:5 |
| Links: |
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| DOI / URN: |
10.1016/j.trim.2016.02.001 |
|---|
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ELV01966303X |
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| 245 | 1 | 0 | |a Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response |
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| 520 | |a Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. | ||
| 520 | |a Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. | ||
| 700 | 1 | |a Wang, Zheng-Yu |4 oth | |
| 700 | 1 | |a Martens, Gregory R. |4 oth | |
| 700 | 1 | |a Ladowski, Joseph M. |4 oth | |
| 700 | 1 | |a Li, Ping |4 oth | |
| 700 | 1 | |a Tector, Matthew |4 oth | |
| 700 | 1 | |a Tector, A. Joseph |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Quinlan-Colwell, Ann ELSEVIER |t Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing |d 2021 |g Amsterdam [u.a.] |w (DE-627)ELV007326742 |
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2016transfer abstract |
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2016 |
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10.1016/j.trim.2016.02.001 doi GBVA2016017000017.pica (DE-627)ELV01966303X (ELSEVIER)S0966-3274(16)30009-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.90 bkl Butler, James R. verfasserin aut Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response 2016transfer abstract 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Wang, Zheng-Yu oth Martens, Gregory R. oth Ladowski, Joseph M. oth Li, Ping oth Tector, Matthew oth Tector, A. Joseph oth Enthalten in Elsevier Quinlan-Colwell, Ann ELSEVIER Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing 2021 Amsterdam [u.a.] (DE-627)ELV007326742 volume:35 year:2016 pages:47-51 extent:5 https://doi.org/10.1016/j.trim.2016.02.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.90 Neurologie VZ AR 35 2016 47-51 5 045F 610 |
| spelling |
10.1016/j.trim.2016.02.001 doi GBVA2016017000017.pica (DE-627)ELV01966303X (ELSEVIER)S0966-3274(16)30009-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.90 bkl Butler, James R. verfasserin aut Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response 2016transfer abstract 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Wang, Zheng-Yu oth Martens, Gregory R. oth Ladowski, Joseph M. oth Li, Ping oth Tector, Matthew oth Tector, A. Joseph oth Enthalten in Elsevier Quinlan-Colwell, Ann ELSEVIER Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing 2021 Amsterdam [u.a.] (DE-627)ELV007326742 volume:35 year:2016 pages:47-51 extent:5 https://doi.org/10.1016/j.trim.2016.02.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.90 Neurologie VZ AR 35 2016 47-51 5 045F 610 |
| allfields_unstemmed |
10.1016/j.trim.2016.02.001 doi GBVA2016017000017.pica (DE-627)ELV01966303X (ELSEVIER)S0966-3274(16)30009-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.90 bkl Butler, James R. verfasserin aut Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response 2016transfer abstract 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Wang, Zheng-Yu oth Martens, Gregory R. oth Ladowski, Joseph M. oth Li, Ping oth Tector, Matthew oth Tector, A. Joseph oth Enthalten in Elsevier Quinlan-Colwell, Ann ELSEVIER Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing 2021 Amsterdam [u.a.] (DE-627)ELV007326742 volume:35 year:2016 pages:47-51 extent:5 https://doi.org/10.1016/j.trim.2016.02.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.90 Neurologie VZ AR 35 2016 47-51 5 045F 610 |
| allfieldsGer |
10.1016/j.trim.2016.02.001 doi GBVA2016017000017.pica (DE-627)ELV01966303X (ELSEVIER)S0966-3274(16)30009-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.90 bkl Butler, James R. verfasserin aut Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response 2016transfer abstract 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Wang, Zheng-Yu oth Martens, Gregory R. oth Ladowski, Joseph M. oth Li, Ping oth Tector, Matthew oth Tector, A. Joseph oth Enthalten in Elsevier Quinlan-Colwell, Ann ELSEVIER Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing 2021 Amsterdam [u.a.] (DE-627)ELV007326742 volume:35 year:2016 pages:47-51 extent:5 https://doi.org/10.1016/j.trim.2016.02.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.90 Neurologie VZ AR 35 2016 47-51 5 045F 610 |
| allfieldsSound |
10.1016/j.trim.2016.02.001 doi GBVA2016017000017.pica (DE-627)ELV01966303X (ELSEVIER)S0966-3274(16)30009-0 DE-627 ger DE-627 rakwb eng 610 610 DE-600 610 VZ 44.90 bkl Butler, James R. verfasserin aut Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response 2016transfer abstract 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. Wang, Zheng-Yu oth Martens, Gregory R. oth Ladowski, Joseph M. oth Li, Ping oth Tector, Matthew oth Tector, A. Joseph oth Enthalten in Elsevier Quinlan-Colwell, Ann ELSEVIER Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing 2021 Amsterdam [u.a.] (DE-627)ELV007326742 volume:35 year:2016 pages:47-51 extent:5 https://doi.org/10.1016/j.trim.2016.02.001 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.90 Neurologie VZ AR 35 2016 47-51 5 045F 610 |
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Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. 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Prescribing and Administering Opioid Doses Based Solely on Pain Intensity: Update of A Position Statement by the American Society for Pain Management Nursing |
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modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig t cell response |
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Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response |
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Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. |
| abstractGer |
Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. |
| abstract_unstemmed |
Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell-mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. Conclusions: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. |
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Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response |
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Wang, Zheng-Yu Martens, Gregory R. Ladowski, Joseph M. Li, Ping Tector, Matthew Tector, A. Joseph |
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