Partial decellularization eliminates immunogenicity in tracheal allografts.

Partial decellularization eliminates immunogenicity in tracheal allografts.
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部分脱细胞消除了气管同种异体移植物中的免疫原性。

DOI:
10.1002/btm2.10525
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发表时间:
2023-09
影响因子:
7.4
通讯作者:
--
中科院分区:
工程技术2区
文献类型:
--
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目前还没有合适的自体组织来桥接较大的气管缺损。因此,对于长段气管重建没有标准的护理。组织工程有可能从同种异体或异种移植物中创造出一种支架,可以支持与天然气管相同的新组织再生。组织工程的最新进展导致了部分脱细胞的想法,允许创建支持气管上皮形成的气管支架,同时保持机械性能。然而,部分脱细胞消除移植物免疫原性的能力尚不清楚,了解部分脱细胞气管移植物(PDTG)的免疫原性是临床转化的关键一步。在这里,我们确定气管同种异体移植物的免疫原性导致上皮细胞脱落并被发育不良的柱状上皮取代,而部分脱细胞产生的移植物能够支持上皮而没有组织学上的排斥迹象。此外,同种异体移植引起CD8+ T细胞浸润,这是一种排斥反应的介质,而PDTG则没有。因此,我们确定部分脱细胞消除同种异体移植物的免疫原性,同时创造一个支架用于植入,可以支持空间适当的气道再生。
There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long‐segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial formation while preserving mechanical properties. However, the ability of partial decellularization to eliminate graft immunogenicity remains unknown, and understanding the immunogenic properties of partially decellularized tracheal grafts (PDTG) is a critical step toward clinical translation. Here, we determined that tracheal allograft immunogenicity results in epithelial cell sloughing and replacement with dysplastic columnar epithelium and that partial decellularization creates grafts that are able to support an epithelium without histologic signs of rejection. Moreover, allograft implantation elicits CD8+ T‐cell infiltration, a mediator of rejection, while PDTG did not. Hence, we establish that partial decellularization eliminates allograft immunogenicity while creating a scaffold for implantation that can support spatially appropriate airway regeneration.
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