Multi-lineage hepatic organoids reveal toxic exosome mediated indirect hepatotoxicity
Researchers developed 3D multi-lineage human hepatic organoids containing five liver cell types and screened 58 drugs, identifying imipramine as an inducer of indirect hepatotoxicity mediated by TrkB activation in hepatic stellate cells. Stellate-cell-derived exosomes become enriched in microRNA-34a-3p, transfer that microRNA to hepatocytes, downregulate XIAP, activate caspase-3, and cause apoptosis; findings were recapitulated in vivo and RNA-seq data are available in SRA.
Why it mattersMicroRNA-34a-3p enrichment in stellate-cell exosomes requires drug developers to screen candidates for indirect hepatotoxicity.