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

Jane Bryant, Kelan A. Hlavaty, Xiaomin Zhang, Woon Teck Yap, Lei Zhang, Lonnie D. Shea, Xunrong Luo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8887-8894
Number of pages8
JournalBiomaterials
Volume35
Issue number31
DOIs
StatePublished - Oct 2014

Keywords

  • 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI)
  • Allogeneic cells
  • Islet
  • Poly(lactide-co-glycolide) (PLG)
  • Tolerance
  • Transplantation

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation'. Together they form a unique fingerprint.

Cite this