Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures
Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures
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DOI：
10.1038/s41598-019-42819-1
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发表时间：
2019-04-23
影响因子：
4.6
通讯作者：
Kim, Carla F.
中科院分区：
文献类型：
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作者：
Leeman, Kristen T.;Pessina, Patrizia;Kim, Carla F.
肺上皮细胞损伤和功能障碍的修复在肺部疾病的发生发展中起着重要作用。有效的修复可能需要肺泡干细胞/祖细胞的正常功能。例如，我们在一只小鼠的支气管肺发育不良(BPD)模型中表明，间充质干细胞(MSC)至少部分通过增加Epcam(+)SCA-1(+)远端肺上皮细胞的数量来保护免受高氧性肺损伤。在三维(3D)器官培养中，这些细胞能够分化为小气道(CCSP+)和肺泡(SPC+)上皮细胞。为了进一步了解MSC和远端肺上皮细胞之间的相互作用，我们将MSC添加到肺祖细胞3D培养中。MSC刺激Epcam(+)、Sca-1(+)衍生器质形成，增加肺泡分化，减少自我更新。MSC条件培养液足以促进肺泡有机样物质的形成，表明MSC分泌的可溶性因子可能是导致这种反应的原因。这项工作为MSC分泌因子对肺祖细胞分化的直接影响提供了强有力的证据。
Lung epithelial cell damage and dysfunctional repair play a role in the development of lung disease. Effective repair likely requires the normal functioning of alveolar stem/progenitor cells. For example, we have shown in a mouse model of bronchopulmonary dysplasia (BPD) that mesenchymal stem cells (MSC) protect against hyperoxic lung injury at least in part by increasing the number of Epcam(+) Sca-1(+) distal lung epithelial cells. These cells are capable of differentiating into both small airway (CCSP+) and alveolar (SPC+) epithelial cells in three-dimensional (3D) organoid cultures. To further understand the interactions between MSC and distal lung epithelial cells, we added MSC to lung progenitor 3D cultures. MSC stimulated Epcam(+) Sca-1(+ )derived organoid formation, increased alveolar differentiation and decreased self-renewal. MSC-conditioned media was sufficient to promote alveolar organoid formation, demonstrating that soluble factors secreted by MSC are likely responsible for the response. This work provides strong evidence of a direct effect of MSC-secreted factors on lung progenitor cell differentiation.