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• W3159881034 abstract "Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a poor prognosis and no cure. Unfortunately, over 90% of drugs fail in clinical trials for IPF due to difficulty in translating promising drugs from animal models. Human precision-cut lung slices (hPCLS) have gained increasing interest as a possible means to model IPF. An early-like stage of IPF can be induced via a fibrosis cocktail (FC) in hPCLS generated from tumor-free cancer resections to study disease and pharmacological approaches. A drawback of using PCLS from tumor-free lung cancer resections is that the tissue can be deranged (<i>e.g.</i> aberrant immune cells and secreted factors), which may contribute to the fibrotic response <i>ex vivo</i>. In the current study, we hypothesized that hPCLS generated from excess donor lung tissue could be used as a more physiologic option. hPCLS were generated from 4 excess donor lungs and treated with FC for up to 120 hours. To obtain non-biased gene expression data, we utilized RNA-seq using an RNA isolation protocol we recently developed. FC induced a fibrotic-like response after 48 hours which increased further with time. Genes associated with matrix remodeling (<i>e.g.</i><i>FN1</i>, <i>COL1A1</i>, and <i>MMP7</i>) and Wnt-signaling (<i>e.g.</i><i>WNT2</i>, <i>WNT5B</i>, <i>WNT10A</i>, <i>NKD1</i>, and <i>AXIN2</i>) increased, whereas genes associated with distal epithelial cell markers (<i>e.g.</i><i>SFTPC</i> and <i>HOPX</i>) decreased. Genes associated with epithelial subtypes in IPF (<i>e.g.</i><i>KRT17</i>) increased. In addition, hPCLS were treated with two novel drugs, one in pre-clinical testing and one currently in Phase II clinical trials for IPF. Each drug induced differential amelioration of fibrotic gene expression, assessed by RNA-seq. hPCLS generated from excess donor lungs and treated with FC are a promising model of IPF and to study potential therapies." @default.
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• W3159881034 date "2021-03-11" @default.
• W3159881034 modified "2023-09-27" @default.
• W3159881034 title "Human precision-cut lung slices generated from excess donor lungs as a model for IPF and drug screening" @default.
• W3159881034 doi "https://doi.org/10.1183/23120541.lsc-2021.106" @default.
• W3159881034 hasPublicationYear "2021" @default.
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