Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
Environmental Health Center, Kangwon National University Hospital, Chuncheon, 24341, South Korea.
Sci Rep. 2019 Jan 24;9(1):505. doi: 10.1038/s41598-018-37193-3.
Human pluripotent stem cell (hPSC)-derived alveolar epithelial cells (AECs) provide new opportunities for understanding lung development and the treatment of pulmonary diseases. However, toxicity assessments using hPSC-AECs have not been undertaken. In this study, we generated functional AECs from hPSCs and evaluated their inflammatory and apoptotic responses to cadmium (Cd) exposure (1, 5, and 10 μM) for 24 h compared with the human bronchial epithelial cell line (BEAS-2B) and primary AECs as controls. Our data showed that Cd (10 μM) treatment induced substantial inflammatory responses and apoptosis in BEAS-2B cells, but not in both hPSC-AECs and primary AECs. Interestingly, conditioned medium from AEC cultures significantly alleviated apoptotic and inflammatory responses to Cd exposure in BEAS-2B cells. Using cytokine arrays, several potential factors secreted from hPSC-AECs and primary AECs were detected and may be involved in reducing Cd-induced cytotoxicity. We also observed higher expression of surfactant proteins B and C in both hPSC-AECs and primary AECs, which may contribute to protection against Cd-induced cytotoxicity. These results suggested that hPSC-AECs phenotypically and functionally resemble primary AECs and could be more biologically relevant alternatives for evaluating the pathological contribution of confirmed or potential pulmotoxic materials included in smoking and microdust.
人多能干细胞（hPSC）衍生的肺泡上皮细胞（AEC）为理解肺发育和治疗肺部疾病提供了新的机会。然而，尚未对 hPSC-AEC 进行毒性评估。在这项研究中，我们从 hPSC 中生成了功能性 AEC，并评估了它们对镉（Cd）暴露（1、5 和 10 μM）24 小时的炎症和凋亡反应，与人类支气管上皮细胞系（BEAS-2B）和原代 AEC 作为对照。我们的数据表明，Cd（10 μM）处理在 BEAS-2B 细胞中诱导了明显的炎症反应和凋亡，但在 hPSC-AEC 和原代 AEC 中均未诱导。有趣的是，AEC 培养物的条件培养基显著减轻了 BEAS-2B 细胞中 Cd 暴露引起的凋亡和炎症反应。通过细胞因子阵列，检测到 hPSC-AEC 和原代 AEC 分泌的几种潜在因子，这些因子可能参与减轻 Cd 诱导的细胞毒性。我们还观察到 hPSC-AEC 和原代 AEC 中表面活性剂蛋白 B 和 C 的表达更高，这可能有助于防止 Cd 诱导的细胞毒性。这些结果表明，hPSC-AEC 在表型和功能上与原代 AEC 相似，并且可能是评估吸烟和微尘中包含的已确认或潜在肺毒性物质的病理贡献的更具生物学相关性的替代方法。
