Alveolar epithelial type II (AT2) cells secrete lung surfactants through lamellar bodies (LBs). Its abnormalities are related to lung diseases, including fibrosis. However, due to a lack of understanding of AT2 cell function, high-content screening (HCS) for LB abnormalities is limited. Recently, researchers have developed LB cells, which have LB-like organelles that secrete surfactant proteins. These cells are more similar to AT2 cells than the parental A549 cells. Recombinant amiodarone (AMD) in LB cells induces LB enlargement, similar to AT2 cells exposed to AMD patients. In order to reverse the LB abnormality induced by amd, the researchers performed HCS on approved drugs and identified 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a potential therapeutic drug. Transcriptome analysis showed that HPβCD regulates lipid homeostasis. In addition, in AT2 cells derived from human induced pluripotent stem cells, HPβCD suppressed amd-induced LB abnormalities. Our results show that LB cells are effective against HCS, and suggest that HPβCD is a drug candidate for the treatment of amd-induced interstitial pneumonia.
It is worth noting that hydroxypropyl beta-cyclodextrin is currently mainly used in pharmaceuticals in the form of excipients. The exploration of API pharmaceutical active ingredients is still in its infancy, but this has opened up a new way of thinking for us. Fine-with a unique structure (hydrophilic outer edge, hydrophobic inner cavity), it is full of broad imagination in the field of drug development.