Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers

Erika M.J. Siren, Haiming D. Luo, Franklin Tam, Ashani Montgomery, Winnie Enns, Haisle Moon, Lyann Sim, Kevin Rey, Qiunong Guan, Jiao Jing Wang, Christine M. Wardell, Mahdis Monajemi, Majid Mojibian, Megan K. Levings, Zheng J. Zhang, Caigan Du, Stephen G. Withers, Jonathan C. Choy, Jayachandran N. Kizhakkedathu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic immunosuppression for the mitigation of immune rejection after organ transplantation causes adverse side effects and constrains the long-term benefits of the transplanted graft. Here we show that protecting the endothelial glycocalyx in vascular allografts via the enzymatic ligation of immunosuppressive glycopolymers under cold-storage conditions attenuates the acute and chronic rejection of the grafts after transplantation in the absence of systemic immunosuppression. In syngeneic and allogeneic mice that received kidney transplants, the steric and immunosuppressive properties of the ligated polymers largely protected the transplanted grafts from ischaemic reperfusion injury, and from immune-cell adhesion and thereby immunocytotoxicity. Polymer-mediated shielding of the endothelial glycocalyx following organ procurement should be compatible with clinical procedures for transplant preservation and perfusion, and may reduce the damage and rejection of transplanted organs after surgery.

Original languageEnglish (US)
JournalNature Biomedical Engineering
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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