Human Lung Organoid Culture in Alginate With and Without Matrigel to Model Development and Disease.
Human Lung Organoid Culture in Alginate With and Without Matrigel to Model Development and Disease.
复制标题
在含有和不含有基质胶的藻酸盐中培养人肺类器官，以模拟发育和疾病。
DOI：
10.1089/ten.tea.2022.0054
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发表时间：
2022
影响因子：
--
通讯作者：
Shea,LonnieD
中科院分区：
文献类型：
--
作者：
Dye,BrianaR;Decker,JosephT;Hein,ReneeFC;Miller,AlyssaJ;Huang,Sha;Spence,JasonR;Shea,LonnieD
人类肺类器官（HLO）通过模拟天然器官组织结构，细胞组成和细胞组织来研究人类肺发育和疾病。在这份报告中，我们证明了HLO来自人多能干细胞培养在藻酸盐，一个完全定义的非动物产品基板，表现出增强的细胞分化相比，HLO培养在市售的基质胶。更具体地说，我们观察到多纤毛细胞的早期出现和数量的增加，沿着粘液产生MUC5AC+杯状细胞，这在基质胶中培养的HLO中没有观察到。藻酸盐生长的HLO中的上皮组织成假复层上皮，气道基底细胞衬在基底层上，但细胞的顶面在类器官的外部。我们进一步观察到，在基质胶中培养的HLO表现出藻酸盐培养物中不存在的间充质过度生长。藻酸盐中HLO内的间充质的容纳使得能够通过用转化生长因子β（TGFβ）治疗来建模特发性肺纤维化（IPF）的关键特征。TGFβ处理导致形态学变化，包括间充质生长增加、IPF标志物表达增加和肺泡样细胞数量减少。该培养系统提供了研究肺发育和疾病状态（如IPF）期间间充质与上皮相互作用的模型。
Human lung organoids (HLOs) are enabling the study of human lung development and disease by modeling native organ tissue structure, cellular composition, and cellular organization. In this report, we demonstrate that HLOs derived from human pluripotent stem cells cultured in alginate, a fully defined nonanimal product substrate, exhibit enhanced cellular differentiation compared with HLOs cultured in the commercially available Matrigel. More specifically, we observed an earlier onset and increase in the number of multiciliated cells, along with mucus producing MUC5AC+goblet-like cells that were not observed in HLOs cultured in Matrigel. The epithelium in alginate-grown HLOs was organized in a pseudostratified epithelium with airway basal cells lining the basal lamina, but with the apical surface of cells on the exterior of the organoid. We further observed that HLOs cultured in Matrigel exhibited mesenchymal overgrowth that was not present in alginate cultures. The containment of the mesenchyme within HLOs in alginate enabled modeling of key features of idiopathic pulmonary fibrosis (IPF) by treatment with transforming growth factor β (TGFβ). TGFβ treatment resulted in morphological changes including an increase in mesenchymal growth, increased expression of IPF markers, and decreased numbers of alveolar-like cells. This culture system provides a model to study the interaction of the mesenchyme with the epithelium during lung development and diseased states such as IPF.
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影响因子：
64.5
作者：
Tim Stuart;Andrew Butler;Paul J. Hoffman;Christoph Hafemeister;Efthymia Papalexi;William M. Mauck;
通讯作者：
Tim Stuart;Andrew Butler;Paul J. Hoffman;Christoph Hafemeister;Efthymia Papalexi;William M. Mauck;
DOI：
10.1165/ajrcmb.10.6.8003339
发表时间：
1994-06-01
影响因子：
6.4
作者：
MERCER, RR;RUSSELL, ML;CRAPO, JD
通讯作者：
CRAPO, JD
影响因子：
29.4
作者：
Dedhia PH;Bertaux-Skeirik N;Zavros Y;Spence JR
通讯作者：
Spence JR
影响因子：
14
作者：
Shikanov, Ariella;Xu, Min;Woodruff, Teresa K.;Shea, Lonnie D.
通讯作者：
Shea, Lonnie D.