1. Surface camouflage of pancreatic islets using 6-arm-PEG-catechol in combined therapy with tacrolimus and anti-CD154 monoclonal antibody for xenotransplantation.
- Author
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Jeong JH, Hong SW, Hong S, Yook S, Jung Y, Park JB, Khue CD, Im BH, Seo J, Lee H, Ahn CH, Lee DY, and Byun Y
- Subjects
- Animals, Antibodies, Monoclonal therapeutic use, Blood Glucose drug effects, Blood Glucose metabolism, Caffeic Acids chemistry, Caffeic Acids therapeutic use, Catechols chemistry, Catechols therapeutic use, Cell Death drug effects, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Experimental therapy, Drug Therapy, Combination, Fasting blood, Fluorescein-5-isothiocyanate metabolism, Glucose pharmacology, Glucose Tolerance Test, Immunohistochemistry, Insulin metabolism, Insulin Secretion, Islets of Langerhans pathology, Male, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Polyethylene Glycols chemistry, Polyethylene Glycols therapeutic use, Rats, Rats, Sprague-Dawley, Surface Properties drug effects, Antibodies, Monoclonal pharmacology, CD40 Ligand immunology, Caffeic Acids pharmacology, Catechols pharmacology, Islets of Langerhans drug effects, Islets of Langerhans Transplantation, Polyethylene Glycols pharmacology, Tacrolimus pharmacology, Transplantation, Heterologous
- Abstract
This study proposes a new combination method of using 6-arm-PEG-catechol to enhance the PEG effect on one hand and another combination of using low doses of Tacrolimus (FK506) and anti-CD154 mAb (MR1) with PEGylation for effective immunoprotection on the other in a xenogenic islet transplantation model. The surface coverage of PEG, viability and functionality of islets were evaluated in vitro, and the effect of surface camouflage on immunoprotection for transplanted islets was evaluated. In addition, the synergistic effects of surface camouflaged islets with low doses of immunosuppressant drugs, such as FK506 and MR1, were evaluated in the xenotransplantation model. The median survival time (MST) of 6-arm-PEG-catechol grafted islets (12.0 ± 1.1 days) was not significantly increased, compared to that of unmodified islets (10.5 ± 1.3 days). However, when 0.2 mg/kg of FK506 was daily administered, the MST of 6-arm-PEG-catechol grafted islet (21.0 ± 1.9 days) was increased twice, compared to that of unmodified islets treated with 0.2 mg/kg of FK506 (10.0 ± 0.9 days). Interestingly, when the recipients of 6-arm-PEG-catechol grafted islets were treated with 0.2 mg/kg of FK506 and 0.1 mg/mouse of MR1, normoglycemia was maintained up to 50 days of transplantation without any fluctuation of glucose level. Therefore, a newly developed protocol using 6-arm-PEG-catechol with FK506 and MR1 would certainly be an effective combination therapy for the treatment of type 1 diabetes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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