In vitro and ex vivo models of human asthma
In vitro and ex vivo models of human asthma
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DOI：
10.1016/j.ejpb.2012.12.014
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发表时间：
2013-06-01
影响因子：
4.9
通讯作者：
Davies, Donna E.
中科院分区：
文献类型：
--
作者：
Blume, Cornelia;Davies, Donna E.
哮喘是一种导气管的炎症性疾病，会经历明显的结构和功能变化，导致非特异性的支气管高反应性(BHR)和随时间波动的气流阻塞。这是一种复杂的疾病，涉及多种遗传和环境影响，其多因素相互作用可导致一系列哮喘表型。由于我们对这些基因-基因和基因-环境相互作用的了解很差，这对“哮喘模型”的逻辑发展提出了重大挑战。然而，使用来自哮喘捐赠者的细胞和组织可以评估遗传和表观遗传学的影响，并在一定程度上反映在活体发生的遗传和环境刺激之间的复杂相互作用。目前体内动物模型的替代方法包括使用大量的系统，从使用单一或联合培养的人类细胞(例如支气管上皮细胞和成纤维细胞)的非常简单的模型，到整个组织外植体(活组织检查、肌条、支气管环)到在体人类志愿者的研究。纤维支气管镜的引入极大地促进了哮喘的研究，纤维支气管镜现在是呼吸系统疾病研究领域的一种常用技术，允许收集活组织标本、支气管刷检样本和支气管肺泡灌洗液，从而能够在其中一些模型中使用疾病来源的细胞和组织。在这里，我们将考虑当前模型的优点和局限性，并讨论组织工程方法的潜力，通过这些方法，我们旨在促进我们对哮喘及其治疗的理解。(C)2013爱思唯尔B.V.保留所有权利。
Asthma is an inflammatory disorder of the conducting airways which undergo distinct structural and functional changes leading to non-specific bronchial hyperresponsiveness (BHR) and airflow obstruction that fluctuate over time. It is a complex disease involving multiple genetic and environmental influences whose multifactorial interactions can result in a range-of asthma phenotypes. Since our understanding of these gene-gene and gene-environment interactions is very poor, this poses a major challenge to the logical development of 'models of asthma'. However, use of cells and tissues from asthmatic donors allows genetic and epigenetic influences to be evaluated and can go some way to reflect the complex interplay between genetic and environmental stimuli that occur in vivo.Current alternative approaches to in vivo animal models involve use of a plethora of systems ranging from very simple models using human cells (e.g. bronchial epithelial cells and fibroblasts) in mono- or co-culture, whole tissue explants (biopsies, muscle strips, bronchial rings) through to in vivo studies in human volunteers. Asthma research has been greatly facilitated by the introduction of fibreoptic bronchoscopy which is now a commonly used technique in the field of respiratory disease research, allowing collection of biopsy specimens, bronchial brushing samples, and bronchoalveolar lavage fluid enabling use of disease-derived cells and tissues in some of these models. Here, we will consider the merits and limitations of current models and discuss the potential of tissue engineering approaches through which we aim to advance our understanding of asthma and its treatment. (C) 2013 Elsevier B.V. All rights reserved.