Differentiated and functional human airway epithelium regeneration in tracheal xenografts
Differentiated and functional human airway epithelium regeneration in tracheal xenografts
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DOI：
10.1152/ajplung.2000.278.1.l165
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发表时间：
2000-01-01
影响因子：
4.9
通讯作者：
Puchelle, E
中科院分区：
文献类型：
--
作者：
Dupuit, F;Gaillard, D;Puchelle, E
为了研究分化良好且功能良好的人气道上皮的再生过程，我们采用了一种体内异种移植模型，在该模型中，成人鼻上皮细胞粘附并逐渐重新填充裸鼠移植的脱皮大鼠气管。利用免疫细胞化学和渗透性示踪剂在光学和超微结构水平上研究了再生过程中再生上皮的增殖活性、分化程度和屏障完整性。裸鼠植入术3天后，气管异种移植物部分再生为扁平的非纤毛和低分化的漏上皮。在移植后第一周结束时，细胞在大鼠气管的整个表面上增殖形成了多层且紧密密封的上皮。在连续几周内，细胞增殖明显减少。此外，上皮逐渐呈柱状、分泌性、纤毛状，并有短暂的渗漏。在4-5周时，重建一个完全分化的假分层功能上皮屏障，该屏障对低分子量示踪剂不渗透。裸鼠气管移植后分化良好的人气道上皮的再生包括几个步骤，模拟了气道上皮损伤后的再生动力学。
To investigate the regeneration process of a well-differentiated and functional human airway epithelium, we adapted an in vivo xenograft model in which adult human nasal epithelial cells adhere and progressively repopulate denuded rat tracheae grafted in nude mice. The proliferating activity, the degree of differentiation, and the barrier integrity of the repopulated epithelium were studied during the regeneration process at optical and ultrastructural levels with immunocytochemistry and a permeability tracer. Three days after implantation in nude mice, tracheal xenografts were partially repopulated with a flattened nonciliated and poorly differentiated leaky epithelium. By the end of the first week after the graft, cell proliferation produced on the entire surface of the rat trachea an epithelium that was stratified into multiple layers and tightly sealed. During successive weeks, cell proliferation dramatically decreased. Moreover, the epithelium became progressively columnar, secretory, ciliated, and transiently leaky. At 4-5 wk, a fully differentiated pseudostratified functional epithelial barrier impermeable to a low-molecular-weight tracer was reconstituted. The regeneration of a well-differentiated and functional human airway epithelium in rat tracheae grafted in nude mice includes several steps that mimic the regeneration dynamics of airway epithelium after injury.