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Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation

Paper ID Volume ID Publish Year Pages File Format Full-Text
5785 430 2014 8 PDF Available
Title
Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation
Abstract

Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation.

Keywords
Allogeneic cells; Islet; Transplantation; Tolerance; 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide (ECDI); Poly(lactide-co-glycolide) (PLG)
First Page Preview
Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 31, October 2014, Pages 8887–8894
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering