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Open Access Liposomal Formulations of Thrombomodulin Increase Engraftment After Intraportal Islet Transplantation

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Abstract:

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- mRNA (p < 0.05), as well as NF-B 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.

Keywords: Engraftment; Inflammation; Islet transplantation; Thrombomodulin; Thrombosis

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368910X513964

Affiliations: Department of Surgery, Emory University, Atlanta, GA, USA

Publication date: November 1, 2010

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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