Electrospun scaffolds limit the regenerative potential of the airway epithelium.
Electrospun scaffolds limit the regenerative potential of the airway epithelium.
复制标题
电纺支架限制了气道上皮的再生潜力。
DOI：
10.1002/lio2.289
复制
发表时间：
2019
影响因子：
1.9
通讯作者：
Reynolds,SusanD
中科院分区：
文献类型：
--
作者：
Schwartz,CynthiaM;Stack,Jacob;Hill,CynthiaL;Lallier,ScottW;Chiang,Tendy;Johnson,Jed;Reynolds,SusanD
显著的发病率和死亡率与合成组织工程气管移植物（TETG）的临床使用相关。我们之前的工作集中在静电纺丝聚对苯二甲酸乙二醇酯和聚氨酯（PET/PU）TETG上，该TETG使用长段气管缺损模型在绵羊中进行了测试。我们报道了移植物狭窄和有限的上皮形成导致移植物失败。本研究确定上皮形成缺陷是否可归因于：1）天然气道基底干细胞/祖细胞的术后耗竭; 2）PET/PU-TETG无法支持上皮迁移;或3）在PET/PU环境中受损的基底干/祖细胞增殖。使用克隆形成细胞频率（CFCF）方法测定接受TETG植入的绵羊中的祖细胞频率。开发了一种模拟上皮向无细胞支架迁移的新型迁移模型，并用于比较上皮向对照聚酯支架和PET/PU支架的迁移。PET/PU支架内的基底干/祖细胞增殖进行了评估，使用CFCF测定，倍增时间分析，和有丝分裂细胞quantitation.ResultsWe报告，TETG植入并没有减少基底干/祖细胞的频率。与此相反，我们发现，上皮细胞向PET/PU支架的迁移明显少于向聚酯支架的迁移，并且PET/PU支架不支持基底干/祖细胞增殖。支架内的祖细胞增殖。证据等级NA
ObjectiveSignificant morbidity and mortality are associated with clinical use of synthetic tissue‐engineered tracheal grafts (TETG). Our previous work focused on an electrospun polyethylene terephthalate and polyurethane (PET/PU) TETG that was tested in sheep using a long‐segment tracheal defect model. We reported that graft stenosis and limited epithelialization contributed to graft failure. The present study determined if the epithelialization defect could be attributed to: 1) postsurgical depletion of native airway basal stem/progenitor cells; 2) an inability of the PET/PU‐TETG to support epithelial migration; or 3) compromised basal stem/progenitor cell proliferation within the PET/PU environment.Study DesignExperimental.MethodsBasal stem/progenitor cell frequency in sheep that underwent TETG implantation was determined using the clone‐forming cell frequency (CFCF) method. A novel migration model that mimics epithelial migration toward an acellular scaffold was developed and used to compare epithelial migration toward a control polyester scaffold and the PET/PU scaffold. Basal stem/progenitor cell proliferation within the PET/PU scaffold was evaluated using the CFCF assay, doubling‐time analysis, and mitotic cell quantification.ResultsWe report that TETG implantation did not decrease basal stem/progenitor cell frequency. In contrast, we find that epithelial migration toward the PET/PU scaffold was significantly less extensive than migration toward a polyester scaffold and that the PET/PU scaffold did not support basal stem/progenitor cell proliferation.ConclusionsWe conclude that epithelialization of a PET/PU scaffold is compromised by poor migration of native tissue‐derived epithelial cells and by a lack of basal stem/progenitor cell proliferation within the scaffold.Level of EvidenceNA