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Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2021-08-09 , DOI: 10.1038/s41551-021-00777-y
Erika M J Siren 1, 2 , Haiming D Luo 1, 2 , Franklin Tam 3 , Ashani Montgomery 3 , Winnie Enns 3 , Haisle Moon 1, 4 , Lyann Sim 2 , Kevin Rey 3 , Qiunong Guan 5 , Jiao-Jing Wang 6 , Christine M Wardell 7, 8 , Mahdis Monajemi 7, 8 , Majid Mojibian 7, 8 , Megan K Levings 7, 8, 9 , Zheng J Zhang 6 , Caigan Du 5 , Stephen G Withers 2 , Jonathan C Choy 3 , Jayachandran N Kizhakkedathu 1, 2, 4, 9
Affiliation  

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.



中文翻译:

通过免疫抑制聚合物保护内皮糖萼预防血管移植排斥反应

用于缓解器官移植后免疫排斥的全身性免疫抑制会导致不良副作用并限制移植物的长期益处。在这里,我们表明在冷藏条件下通过免疫抑制性糖聚合物的酶促连接保护血管同种异体移植物中的内皮糖萼可减轻移植后在没有全身免疫抑制的情况下移植物的急性和慢性排斥反应。在接受肾移植的同基因和同种异体小鼠中,结扎聚合物的空间位阻和免疫抑制特性在很大程度上保护了移植的移植物免受缺血再灌注损伤、免疫细胞粘附和免疫细胞毒性的影响。

更新日期:2021-08-09
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