Developing a tissue-engineered model of the human bronchiole
Developing a tissue-engineered model of the human bronchiole
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DOI：
10.1002/term.277
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发表时间：
2010-12-01
影响因子：
3.3
通讯作者：
Niklason, Laura
中科院分区：
文献类型：
--
作者：
Miller, Cheryl;George, Steven;Niklason, Laura
科学家们一直在寻找新的工具来更好地模拟人体解剖学和生理学，特别是研究慢性呼吸道疾病。气道重塑是哮喘的主要特征，并与慢性气道炎症同时发生。炎症和修复过程都改变了气道壁，其特征是解剖、生理和功能的改变。细支气管重建的组织工程模型为研究气道重建的开始和进展提供了一种新的方法。通过开发一种独特的生物反应器系统，由特征良好的人肺原代细胞构建的圆柱形细支气管已经被设计和检查，对实验变量有了更大的控制。我们培养了由成纤维细胞、气道平滑肌细胞、小气道上皮细胞和细胞外基质组成的人细支气管。各种细胞类型在细胞信号传导和基质相互作用中彼此接近。组织的圆柱形几何形状为机械转导提供径向膨胀，空气界面为上皮细胞提供自然环境。确定最佳细胞密度、细胞外基质浓度和培养基组成。免疫组织化学证实细支气管表型稳定。静息是通过蛋白表达来测定的，这证实了在初始制造阶段和空气界面实施后表型的变化。设计了一个制造时间表，用于重复细支气管制造，并了解组织收缩和细胞播种时间。细支气管结构及其细胞组成的稳定性使这些细支气管能够研究细胞间的相互作用和重塑事件，同时保持体内的几何尺寸和关系。版权所有John Wiley & Sons， Ltd。
Scientists are always looking for new tools to better mimic human anatomy and physiology, especially to study chronic respiratory disease. Airway remodelling is a predominant feature in asthma and occurs in conjunction with chronic airway inflammation. Both the inflammatory and repair processes alter the airway wall which is marked by anatomical, physiological and functional changes. A tissue-engineered model of bronchiole remodelling presents a novel approach to investigating the initiation and progression of airway remodelling. By developing a unique bioreactor system, cylindrical-shaped bronchioles constructed from well-characterized human lung primary cells have been engineered and examined with a much greater control over experimental variables. We have grown human bronchioles composed of fibroblasts, airway smooth muscle cells, small airway epithelial cells and extracellular matrices. The various cell types are in close proximity to one another for cell cell signalling and matrix interactions. The cylindrical geometry of the tissue applies radial distension for mechanotransduction and the air interface provides a natural environment for the epithelial cells. Optimal cell density, extracellular matrix concentration and media composition were determined. Immunohistochemistry verified bronchiole phenotypic stability. Quiescence was gauged by protein expression which verified a change in phenotype after the initial fabrication stage and implementation of the air interface. A fabrication timeline was devised for repeatable bronchiole fabrication and to understand tissue contraction and cell-seeding duration. The stability of the bronchiole structures and their cellular composition lends these bronchioles to study cell cell interactions and remodelling events while maintaining in vivo geometrical dimensions and relationships. Copyright (C) 2010 John Wiley & Sons, Ltd.