Journal
NATURE BIOMEDICAL ENGINEERING
Volume 5, Issue 10, Pages 1202-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41551-021-00777-y
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Funding
- Canadian Institutes of Health Research (CIHR) [CIHR FDN-154304]
- Natural Sciences and Engineering Council of Canada (NSERC)
- Heart and Stroke Foundation of Canada
- Canadian Glycomics Network of Centres of Excellence, GlycoNet
- Canada Foundation for Innovation (CFI)
- British Columbia Knowledge Development Fund (BCKDF)
- Michael Smith Foundation for Health Research (MSFHR)
- Centre for Blood Research graduate award
- NSERC CGS-M
- NSERC CREATE NanoMat Program
- NSERC PGS-D
- Canadian Blood Services
- BC Children's Hospital Research Institute
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Protecting the endothelial glycocalyx in vascular allografts via the enzymatic ligation of immunosuppressive glycopolymers can attenuate acute and chronic rejection of the grafts after transplantation, without the need for systemic immunosuppression.
Protection of the endothelial glycocalyx in vascular allografts via the enzymatic ligation of immunosuppressive glycopolymers prevents allograft rejection after transplantation in the absence of systemic immunosuppression. 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.
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