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Siren EMJ, Luo HD, Tam F, et al. Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers. Nat Biomed Eng. 2021;5(10):1202-1216doi: 10.1038/s41551-021-00777-y.
Siren, E. M. J., Luo, H. D., Tam, F., Montgomery, A., Enns, W., Moon, H., Sim, L., Rey, K., Guan, Q., Wang, J. J., Wardell, C. M., Monajemi, M., Mojibian, M., Levings, M. K., Zhang, Z. J., Du, C., Withers, S. G., Choy, J. C., & Kizhakkedathu, J. N. (2021). Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers. Nature biomedical engineering, 5(10), 1202-1216. https://doi.org/10.1038/s41551-021-00777-y
Siren, Erika M J, et al. "Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers." Nature biomedical engineering vol. 5,10 (2021): 1202-1216. doi: https://doi.org/10.1038/s41551-021-00777-y
Siren EMJ, Luo HD, Tam F, Montgomery A, Enns W, Moon H, Sim L, Rey K, Guan Q, Wang JJ, Wardell CM, Monajemi M, Mojibian M, Levings MK, Zhang ZJ, Du C, Withers SG, Choy JC, Kizhakkedathu JN. Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers. Nat Biomed Eng. 2021 Oct;5(10):1202-1216. doi: 10.1038/s41551-021-00777-y. Epub 2021 Aug 09. PMID: 34373602.
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Nat Biomed Eng. 2021 Oct;5(10):1202-1216. doi: 10.1038/s41551-021-00777-y. Epub 2021 Aug 09.

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

Nature biomedical engineering

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

Affiliations

  1. Centre for Blood Research, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
  2. Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada.
  3. Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
  4. Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
  5. Department of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
  6. Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA.
  7. BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  8. Department of Surgery, The University of British Columbia, Vancouver, British Columbia, Canada.
  9. School of Biomedical Engineering, The University of British Columbia, Vancouver, British Columbia, Canada.
  10. Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. [email protected].
  11. Centre for Blood Research, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada. [email protected].
  12. Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada. [email protected].
  13. Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. [email protected].
  14. School of Biomedical Engineering, The University of British Columbia, Vancouver, British Columbia, Canada. [email protected].

PMID: 34373602 DOI: 10.1038/s41551-021-00777-y

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.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

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