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

Publication ,  Journal Article
Bryant, J; Hlavaty, KA; Zhang, X; Yap, W-T; Zhang, L; Shea, LD; Luo, X
Published in: Biomaterials
October 2014

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.

Duke Scholars

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Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

October 2014

Volume

35

Issue

31

Start / End Page

8887 / 8894

Location

Netherlands

Related Subject Headings

  • Transplantation, Homologous
  • Sirolimus
  • Polyglactin 910
  • Nanoparticles
  • Mice, Inbred BALB C
  • Male
  • Islets of Langerhans Transplantation
  • Immunosuppressive Agents
  • Immune Tolerance
  • Ethyldimethylaminopropyl Carbodiimide
 

Citation

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Bryant, J., Hlavaty, K. A., Zhang, X., Yap, W.-T., Zhang, L., Shea, L. D., & Luo, X. (2014). Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation. Biomaterials, 35(31), 8887–8894. https://doi.org/10.1016/j.biomaterials.2014.06.044
Bryant, Jane, Kelan A. Hlavaty, Xiaomin Zhang, Woon-Teck Yap, Lei Zhang, Lonnie D. Shea, and Xunrong Luo. “Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.Biomaterials 35, no. 31 (October 2014): 8887–94. https://doi.org/10.1016/j.biomaterials.2014.06.044.
Bryant J, Hlavaty KA, Zhang X, Yap W-T, Zhang L, Shea LD, et al. Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation. Biomaterials. 2014 Oct;35(31):8887–94.
Bryant, Jane, et al. “Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.Biomaterials, vol. 35, no. 31, Oct. 2014, pp. 8887–94. Pubmed, doi:10.1016/j.biomaterials.2014.06.044.
Bryant J, Hlavaty KA, Zhang X, Yap W-T, Zhang L, Shea LD, Luo X. Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation. Biomaterials. 2014 Oct;35(31):8887–8894.
Journal cover image

Published In

Biomaterials

DOI

EISSN

1878-5905

Publication Date

October 2014

Volume

35

Issue

31

Start / End Page

8887 / 8894

Location

Netherlands

Related Subject Headings

  • Transplantation, Homologous
  • Sirolimus
  • Polyglactin 910
  • Nanoparticles
  • Mice, Inbred BALB C
  • Male
  • Islets of Langerhans Transplantation
  • Immunosuppressive Agents
  • Immune Tolerance
  • Ethyldimethylaminopropyl Carbodiimide