Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation
Early destruction of donor islet grafts due to an instant blood-mediated inflammatory reaction (IBMIR) remains a major obstacle in islet transplantation. Thrombomodulin plays an important role in limiting coagulation and inflammatory events through a variety of effects. In this study, we investigate...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2010-11-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X513964 |
| _version_ | 1819206714562445312 |
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| author | Wanxing Cui Julianty Angsana Jing Wen Elliot L. Chaikof M.D., Ph.D. |
| author_facet | Wanxing Cui Julianty Angsana Jing Wen Elliot L. Chaikof M.D., Ph.D. |
| author_sort | Wanxing Cui |
| collection | DOAJ |
| description | Early destruction of donor islet grafts due to an instant blood-mediated inflammatory reaction (IBMIR) remains a major obstacle in islet transplantation. Thrombomodulin plays an important role in limiting coagulation and inflammatory events through a variety of effects. In this study, we investigated the ability of thrombomodulin (TM), when reconstituted as a liposomal formulation, to enhance early syngeneic islet engraftment by minimizing or abrogating the IBMIR. Administration of TM significantly improved early engraftment of syngeneic islets after intraportal transplantation in diabetic mice. In the absence of treatment, conversion to euglycemia was observed among 46.6% (7/15) of recipients. In contrast, administration of TM led to euglycemia in 93.3% (14/15) of recipients ( p = 0.0142). Recipients that received TM exhibited a lower incidence of primary nonfunction and better glucose control over a 30-day period after transplantation. Fibrin deposition ( p < 0.05), neutrophil infiltration ( p < 0.05), expression of TNF-α and IL-β mRNA ( p < 0.05), as well as NF-κB activity ( p < 0.05) were significantly reduced in the liver of islet recipients having been treated with liposomal TM. These data demonstrate that TM significantly improves early syngeneic islet engraftment through effects that target both coagulation and inflammatory pathways. |
| first_indexed | 2024-12-23T05:11:59Z |
| format | Article |
| id | doaj.art-e4d969f156094865b8d82c747f0c8481 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-23T05:11:59Z |
| publishDate | 2010-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-e4d969f156094865b8d82c747f0c84812022-12-21T17:58:57ZengSAGE PublishingCell Transplantation0963-68971555-38922010-11-011910.3727/096368910X513964Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet TransplantationWanxing Cui0Julianty Angsana1Jing Wen2Elliot L. Chaikof M.D., Ph.D.3Department of Surgery, Emory University, Atlanta, GA, USADepartment of Biomedical Engineering, Emory University/Georgia Institute of Technology, Atlanta, GA, USADepartment of Surgery, Emory University, Atlanta, GA, USASchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USAEarly destruction of donor islet grafts due to an instant blood-mediated inflammatory reaction (IBMIR) remains a major obstacle in islet transplantation. Thrombomodulin plays an important role in limiting coagulation and inflammatory events through a variety of effects. In this study, we investigated the ability of thrombomodulin (TM), when reconstituted as a liposomal formulation, to enhance early syngeneic islet engraftment by minimizing or abrogating the IBMIR. Administration of TM significantly improved early engraftment of syngeneic islets after intraportal transplantation in diabetic mice. In the absence of treatment, conversion to euglycemia was observed among 46.6% (7/15) of recipients. In contrast, administration of TM led to euglycemia in 93.3% (14/15) of recipients ( p = 0.0142). Recipients that received TM exhibited a lower incidence of primary nonfunction and better glucose control over a 30-day period after transplantation. Fibrin deposition ( p < 0.05), neutrophil infiltration ( p < 0.05), expression of TNF-α and IL-β mRNA ( p < 0.05), as well as NF-κB activity ( p < 0.05) were significantly reduced in the liver of islet recipients having been treated with liposomal TM. These data demonstrate that TM significantly improves early syngeneic islet engraftment through effects that target both coagulation and inflammatory pathways.https://doi.org/10.3727/096368910X513964 |
| spellingShingle | Wanxing Cui Julianty Angsana Jing Wen Elliot L. Chaikof M.D., Ph.D. Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation Cell Transplantation |
| title | Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation |
| title_full | Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation |
| title_fullStr | Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation |
| title_full_unstemmed | Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation |
| title_short | Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation |
| title_sort | liposomal formulations of thrombomodulin increase engraftment after intraportal islet transplantation |
| url | https://doi.org/10.3727/096368910X513964 |
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