Prevention of the second stage of epithelial loss is a potential novel treatment for bronchiolitis obliterans.
Prevention of the second stage of epithelial loss is a potential novel treatment for bronchiolitis obliterans.
复制标题
预防第二阶段上皮损失是闭塞性细支气管炎的一种潜在的新型治疗方法。
DOI：
10.1016/j.jtcvs.2012.07.098
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Lau,ChristineL
中科院分区：
文献类型：
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作者：
Zhao,Yunge;Steidle,JohnF;Upchurch,GilbertR;Kron,IrvingL;Lau,ChristineL
上皮细胞的缺失是导致气道纤维化的关键因素之一。上皮细胞的损失可能降低宿主细胞浸润到管腔中的屏障，允许细胞外基质沉积，随后导致气道闭塞。本研究的目的是确定是否从受体的上皮细胞/祖细胞注射到管腔的供体气管可以防止闭塞性细支气管炎（BO）在小鼠异位气管移植（HTT）model.METHODSA主要组织相容性复合物I类和II类错配的小鼠HTT模型BO。从受体小鼠中分离上皮细胞，并在移植后第3天重新注射到同种异体移植物的管腔中。Rag-1敲除和同种移植物也作为对照进行。结果表明，气管上皮细胞在第3天丢失，在3至7天之间再生，并且在所有同种异体移植物中再次丢失，但在同系移植物或Rag-1敲除组中在第12天未丢失。基于绿色荧光蛋白染色，重建的上皮是第7天来源于供体的。此外，与受体细胞注射到气管腔，上皮细胞的损失没有观察到和管腔闭塞显着减少allografts.CONCLUSIONSInjection受体上皮细胞防止第二阶段的上皮损失，并显着降低BO的发展在HTT模型。在临床上，使用注射受体上皮细胞可能是BO的一种新治疗方法。
OBJECTIVESLoss of epithelial cells is one of the key factors that lead to airway fibrosis. Loss of epithelial cells may decrease the barrier to host cell infiltration into the lumen, allowing deposition of extracellular matrix, with subsequent obliteration of the airway. The objective of this study was to determine whether injection of epithelial cells/progenitor cells from the recipient into the lumen of the donor trachea could prevent bronchiolitis obliterans (BO) in a mouse heterotopic tracheal transplantation (HTT) model.METHODSA major histocompatibility complex class I and class II mismatch of mouse HTT model of BO was used. Epithelial cells from recipient mice were isolated and reinjected into the lumen of the allografts on day 3 after transplantation. Rag-1 knock-out and isografts were also performed as controls. The grafts were analyzed by immunohistochemistry and densitometric analysis.RESULTSThe results demonstrated that tracheal epithelium was lost by day 3, regenerated between 3 to 7 days, and was lost again in all allografts, but not in the isografts or in Rag-1 knock-out groups by day 12. The reconstituted epithelium was donor originated on day 7 based on green fluorescent protein staining. Furthermore, with the injection of recipient cells into the tracheal lumen, loss of the epithelium was not observed and the luminal obliteration was significantly less in the allografts.CONCLUSIONSInjection of recipient epithelial cells prevents the second phase of epithelial loss and significantly decreases BO development in an HTT model. Clinically, the use of injected recipient epithelial cells could be a novel treatment for BO.