Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.
Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.
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DOI：
10.1371/journal.pone.0110195
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Pérez-Gil J
中科院分区：
文献类型：
--
作者：
Cerrada A;de la Torre P;Grande J;Haller T;Flores AI;Pérez-Gil J
肺泡II型（ATII）细胞专门合成和分泌肺表面活性物质，这是一种脂质-蛋白质复合物，可降低表面张力以最大限度地减少呼吸功。表面活性剂的合成、组装和分泌受到密切调节，其受损与严重的呼吸系统疾病有关。目前，还没有完善的ATII细胞培养模型。在这项工作中，蜕膜来源的间充质干细胞（DMSC）已经分化成肺泡II型样细胞（ATII-LC），其显示类似板层体的膜质细胞器，该细胞器参与天然ATII细胞的表面活性剂储存和分泌，并积累二饱和磷脂物质，表面活性剂标志。在基因和蛋白质水平上证明ATII细胞特征性标志物在ATII-LC中的表达。模仿ATII细胞对促分泌素的反应，ATII-LC能够使富含脂质的组装体胞吐，其显示出高度的表面活性能力，包括比标准天然表面活性剂更快的界面吸附动力学，即使在抑制剂存在下也是如此。ATII-LCs可以构成一个非常有用的离体模型，用于研究表面活性剂的生物合成和参与蛋白质加工和脂质运输的机制，以及表面活性剂复合物的包装和储存。
Lung alveolar type II (ATII) cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs) have been differentiated into Alveolar Type II- Like Cells (ATII-LCs), which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.
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DOI：
10.1152/ajplung.00342.2003
发表时间：
2004-05-01
影响因子：
4.9
作者：
Haller, T;Dietl, P;Putz, G
通讯作者：
Putz, G
影响因子：
3.5
作者：
Canals, Daniel;Mormeneo, David;Delgado, Antonio
通讯作者：
Delgado, Antonio
影响因子：
--
作者：
Jennings, P;Bertocchi, C;Dietl, P
通讯作者：
Dietl, P
DOI：
10.1073/pnas.95.4.1579
发表时间：
1998-02-17
影响因子：
11.1
作者：
Haller, T;Ortmayr, J;Dietl, P
通讯作者：
Dietl, P
影响因子：
3.9
作者：
Ma, Nan;Gai, Hui;Zhong, Hong
通讯作者：
Zhong, Hong