Procedure for Lung Engineering
Procedure for Lung Engineering
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DOI：
10.3791/2651
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发表时间：
2011-03-01
影响因子：
1.2
通讯作者：
Niklason, Laura E.
中科院分区：
文献类型：
--
作者：
Calle, Elizabeth A.;Petersen, Thomas H.;Niklason, Laura E.
肺组织，包括肺癌和慢性肺部疾病，如慢性阻塞性肺病，每年累计造成约280，000人死亡;慢性阻塞性肺病目前是美国第四大死亡原因（1）。导致这种死亡率的原因是肺通常不能在微观细胞水平上修复或再生。因此，因变性或感染而受损的肺组织或手术切除的肺组织在体内不能被功能性替代。为了探索肺组织是否可以在体外产生，我们使用去除细胞成分以产生脱细胞肺细胞外基质支架的程序处理来自成年大鼠的肺。这种支架保留了气道和脉管系统的分级分支结构，以及基本上完整的基底膜，其包含胶原蛋白IV、层粘连蛋白和纤连蛋白。该支架安装在生物反应器中，该生物反应器设计用于模拟肺生理学的关键方面，例如负压通气和脉动血管灌注。通过在生物反应器安装的支架内培养肺上皮和血管内皮，我们能够产生与天然肺组织表型相当并且能够在短时间间隔（45-120分钟）内参与气体交换的肺组织。这些结果是令人鼓舞的，并表明肺基质的再增殖是肺再生的可行策略。这种可能性提供了一个机会，不仅可以努力增加肺组织的供应，用于移植，而且可以在体外研究呼吸细胞和分子生物学，时间更长，并且比以前更精确的微环境。
Lung tissue, including lung cancer and chronic lung diseases such as chronic obstructive pulmonary disease, cumulatively account for some 280,000 deaths annually; chronic obstructive pulmonary disease is currently the fourth leading cause of death in the United States(1). Contributing to this mortality is the fact that lungs do not generally repair or regenerate beyond the microscopic, cellular level. Therefore, lung tissue that is damaged by degeneration or infection, or lung tissue that is surgically resected is not functionally replaced in vivo. To explore whether lung tissue can be generated in vitro, we treated lungs from adult rats using a procedure that removes cellular components to produce an acellular lung extracellular matrix scaffold. This scaffold retains the hierarchical branching structures of airways and vasculature, as well as a largely intact basement membrane, which comprises collagen IV, laminin, and fibronectin. The scaffold is mounted in a bioreactor designed to mimic critical aspects of lung physiology, such as negative pressure ventilation and pulsatile vascular perfusion. By culturing pulmonary epithelium and vascular endothelium within the bioreactor-mounted scaffold, we are able to generate lung tissue that is phenotypically comparable to native lung tissue and that is able to participate in gas exchange for short time intervals (45-120 minutes). These results are encouraging, and suggest that repopulation of lung matrix is a viable strategy for lung regeneration. This possibility presents an opportunity not only to work toward increasing the supply of lung tissue for transplantation, but also to study respiratory cell and molecular biology in vitro for longer time periods and in a more accurate microenvironment than has previously been possible.