Tracheal Macrophages During Regeneration and Repair of Long-Segment Airway Defects.
Tracheal Macrophages During Regeneration and Repair of Long-Segment Airway Defects.
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长段气道缺损再生和修复过程中的气管巨噬细胞。
DOI：
10.1002/lary.29698
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Chiang T
中科院分区：
文献类型：
--
作者：
Tan ZH;Dharmadhikari S;Liu L;Wolter G;Shontz KM;Reynolds SD;Johnson J;Breuer CK;Chiang T
组织工程气管移植物（TETG）为修复长段气道缺损提供了一种潜在的解决方案。然而，临床前和临床tetg与慢性炎症和巨噬细胞浸润有关。巨噬细胞表现出很大的表型异质性（通常表征为经典活化（M1）和替代活化（M2）），并能影响气管修复和再生。我们使用小鼠气管显微外科模型对浸润的宿主巨噬细胞进行量化和表征。我们评估了同种气管移植物、合成tetg或部分去细胞化气管支架（DTS）植入动物的巨噬细胞浸润和表型。同种气管置换后观察到巨噬细胞浸润。原生气管中均存在M1和M2巨噬细胞，且在气管修复早期均有所增加（p=0.014）， M1/M2比值为0.48±0.15。相比之下，原位植入合成TETG导致巨噬细胞表型向M1为主转移，在植入后6周M1/M2比增加1.35±0.41 （p=0.035）。添加聚乙醇酸（PGA）调节合成支架后，由于M2巨噬细胞增加，M1/M2比值降低（p=0.006）。使用系统性巨噬细胞消耗，合成TETG受体的M1/M2比率恢复到天然值，并与移植物上皮化增加有关。DTS中巨噬细胞比例与天然值相近。在气管修复过程中存在M1和M2巨噬细胞。合成TETG的上皮化不良与M1/M2比值升高有关。巨噬细胞表型可以通过支架组成和宿主定向的全身治疗来改变。DTS的M1/M2比率与天然气管和同系气管置换术相似。N/A
Tissue-engineered tracheal grafts(TETG) offer a potential solution for repair of long-segment airway defects. However, pre-clinical and clinical TETGs have been associated with chronic inflammation and macrophage infiltration. Macrophages express great phenotypic heterogeneity (generally characterized as classically-activated(M1) vs. alternatively-activated(M2)) and can influence tracheal repair and regeneration. We quantified and characterized infiltrating host macrophages using mouse microsurgical tracheal replacement models. We assessed macrophage infiltration and phenotype in animals implanted with syngeneic tracheal grafts, synthetic TETGs or partially decellularized tracheal scaffolds(DTS). Macrophage infiltration was observed following tracheal replacement with syngeneic trachea. Both M1 and M2 macrophages were present in native trachea and increased during early tracheal repair(p=0.014), with an M1/M2 ratio of 0.48±0.15. In contrast, orthotopic implantation of synthetic TETG resulted in a shift to M1 predominant macrophage phenotype with an increased M1/M2 ratio of 1.35±0.41 by 6 weeks following implant(p=0.035). Modulation of the synthetic scaffold with the addition of polyglycolic acid(PGA) resulted in a reduction of M1/M2 ratio due to an increase in M2 macrophages(p=0.006). Using systemic macrophage depletion, M1/M2 ratio reverted to native values in synthetic TETG recipients and was associated with an increase in graft epithelialization. Macrophage ratio seen in DTS were similar to native values. M1 and M2 macrophages are present during tracheal repair. Poor epithelialization with synthetic TETG is associated with an elevation of the M1/M2 ratio. Macrophage phenotype can be altered with scaffold composition and host-directed systemic therapies. DTS exhibit M1/M2 ratios similar to those seen in native trachea and syngeneic tracheal replacement. N/A
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影响因子：
23.9
作者：
Lechner AJ;Driver IH;Lee J;Conroy CM;Nagle A;Locksley RM;Rock JR
通讯作者：
Rock JR
影响因子：
4.6
作者：
Becker M;De Bastiani MA;Parisi MM;Guma FT;Markoski MM;Castro MA;Kaplan MH;Barbé-Tuana FM;Klamt F
通讯作者：
Klamt F
影响因子：
3
作者：
Batioglu-Karaaltin A;Ovali E;Karaaltin MV;Yener M;Yılmaz M;Eyüpoğlu F;Yılmaz YZ;Bozkurt ER;Demir N;Konuk E;Bozdağ ES;Yiğit Ö;Cansiz H
通讯作者：
Cansiz H
影响因子：
8.8
作者：
Engler AE;Ysasi AB;Pihl RMF;Villacorta-Martin C;Heston HM;Richardson HMK;Thapa BR;Moniz NR;Belkina AC;Mazzilli SA;Rock JR
通讯作者：
Rock JR
影响因子：
8
作者：
Hung LY;Sen D;Oniskey TK;Katzen J;Cohen NA;Vaughan AE;Nieves W;Urisman A;Beers MF;Krummel MF;Herbert DR
通讯作者：
Herbert DR