Novel in vitro respiratory models to study lung development, physiology, pathology and toxicology.

Novel in vitro respiratory models to study lung development, physiology, pathology and toxicology.
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DOI:
10.1186/scrt368
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发表时间:
2013
影响因子:
7.5
通讯作者:
Cortiella J
Cortiella J
中科院分区:
医学2区
文献类型:
--
作者:
Nichols JE;Niles JA;Vega SP;Cortiella J

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在急性肺损伤或呼吸窘迫发展过程中,对患者肺病理的详细研究是有限的,过去与肺特异性反应相关的信息来自尸检死亡患者或动物模型的肺研究。良好的体外人体组织模型的发展将有助于弥合我们目前对肺反应知识的差距,并提供对肺发育、生理和病理的更好理解。简单的单细胞或双细胞培养系统以及复杂的多细胞肺类似物的体外模型已经实现,这些模型可以复制特定人类肺反应的定义成分。目前体外肺模型的一个好处是,从人类或动物疾病研究的数据回顾中产生的假设可以直接在工程人体组织模型中进行测试。使用简单的体外肺系统或更复杂的三维模型进行的研究结果已经用于检查基于细胞的反应、生理功能、病理变化甚至药物毒性或药物反应。在未来,我们将创建具有特定遗传概况的模型,以测试单个基因产物或重要途径的重要性。支持高通量筛选的基于微流体的模型的最新发展将允许在人体系统中进行早期毒性测试,并更快地开发新的和创新的医疗产品。未来的模型设计还将允许同时评估多个器官系统,提供一种更全面或全身的方法来理解人体生理学和反应。
Detailed studies of lung pathology in patients during the course of development of acute lung injury or respiratory distress are limited, and in the past information related to lung-specific responses has been derived from the study of lungs from patients who died at autopsy or from animal models. Development of good in vitro human tissue models would help to bridge the gap in our current knowledge of lung responses and provide a better understanding of lung development, physiology and pathology. In vitro models of simple one-cell or two-cell culture systems as well as complex multicellular lung analogs that reproduce defined components of specific human lung responses have already been realized. A benefit of current in vitro lung models is that hypotheses generated from review of data from human or animal disease studies can be tested directly in engineered human tissue models. Results of studies done using simple in vitro lung systems or more complex three-dimensional models have already been used to examine cell-based responses, physiologic functions, pathologic changes and even drug toxicity or drug responses. In the future we will create models with specific genetic profiles to test the importance of single gene products or pathways of significance. Recent development of microfluidics-based models that support high-throughput screening will allow early-stage toxicity testing in human systems and faster development of new and innovative medical products. Model design in the future will also allow for evaluation of multiple organ systems at once, providing a more holistic or whole-body approach to understanding human physiology and responses.
来自小鼠ESC和患者特异性囊性纤维化IPSC的多态肺和气道祖细胞产生。
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