Immune characterization of a xenogeneic human lung cross-circulation support system.

Immune characterization of a xenogeneic human lung cross-circulation support system.
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DOI:
10.1126/sciadv.ade7647
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发表时间:
2023-03-31
期刊:
影响因子:
13.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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对于不断增长的终末期肺病患者,迫切需要改进方法来扩大适合移植的供体肺库。先前已经报道了猪和移植的人肺之间的全血交叉循环(XC)能够体外恢复由于急性可逆损伤而拒绝移植的供体肺。然而,这种异种平台的免疫相互作用尚未被表征,从而限制了潜在的翻译应用。使用流式细胞术和免疫组织化学,我们证明在基于钙调神经磷酸酶的免疫抑制和补体消耗的背景下,猪免疫细胞和免疫球蛋白浸润发生在该异种XC系统中。尽管如此,异种XC在异种支持的24小时内支持人供体肺的活力、组织完整性和生理改善。这些发现为未来的免疫调节策略提供了目标,以最大限度地减少该器官支持生物技术的免疫相互作用。异种交叉循环过程中的细胞和体液免疫相互作用是翻译的免疫调节靶点。
Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed for the growing population with end-stage lung disease. Cross-circulation (XC) of whole blood between swine and explanted human lungs has previously been reported to enable the extracorporeal recovery of donor lungs that declined for transplantation due to acute, reversible injuries. However, immunologic interactions of this xenogeneic platform have not been characterized, thus limiting potential translational applications. Using flow cytometry and immunohistochemistry, we demonstrate that porcine immune cell and immunoglobulin infiltration occurs in this xenogeneic XC system, in the context of calcineurin-based immunosuppression and complement depletion. Despite this, xenogeneic XC supported the viability, tissue integrity, and physiologic improvement of human donor lungs over 24 hours of xeno-support. These findings provide targets for future immunomodulatory strategies to minimize immunologic interactions on this organ support biotechnology. Cellular and humoral immune interactions during xenogeneic cross-circulation are immunomodulatory targets for translation.
眼镜蛇毒因子诱导的补体耗竭通过减轻血气屏障损伤来预防肺缺血再灌注损伤
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