In vivo models of human airway epithelium repair and regeneration
In vivo models of human airway epithelium repair and regeneration
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DOI：
10.1183/09059180.05.00009702
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发表时间：
2005-12-01
影响因子：
7.5
通讯作者：
Puchelle, E.
中科院分区：
文献类型：
--
作者：
Coraux, C.;Hajj, R.;Puchelle, E.
尽管有有效的防御系统，但与外部环境永久接触的气道表面上皮经常受到吸入污染物、微生物和病毒的损伤。气道表面上皮对急性损伤的反应包括一系列细胞事件，从表面上皮完整性的丧失到上皮的部分脱落，甚至到基底膜的完全剥脱。然后上皮必须修复和再生以恢复其功能。动物模型上皮再生的体内研究表明，气道上皮细胞能够去分化、扩散、在裸露的基底膜上迁移，并在几周后逐渐重新分化以重建功能性呼吸道上皮。在免疫缺陷裸鼠和严重联合免疫缺陷（SCID）小鼠中开发了人源化气管异种移植模型，以模拟人气道上皮的自然再生过程并分析细胞和气道上皮重建不同步骤中涉及的分子事件。这些模型代表了非常强大的工具，用于分析上皮再生过程中生物功能的调节。它们对于识别人类气道上皮的干/祖细胞也非常有用。更好地了解气道上皮再生的机制，以及上皮干细胞和祖细胞的特征，可能为再生治疗铺平道路，从而在许多呼吸系统疾病中重建功能性气道上皮，例如哮喘、慢性阻塞性肺病、囊性纤维化和细支气管炎。
Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks.Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID) mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium.A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.