biostudies-literatureHartauer MDefense Threat Reduction AgencyNCRR NIH HHSNIEHS NIH HHSNCI NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSNIH HHS50https://www.ebi.ac.uk/biostudies/studies/S-EPMC12804587biostudies-literatureUnknown83(1)There is growing demand for improved in vitro liver models to better predict in vivo pharmacology, specifically drug disposition mediated by hepatic transporters and assessment of transporter-mediated drug interaction risk. While 2D sandwich-cultured human hepatocytes (SCHH) remain valuable, they are limited to short-term use due to hepatocyte de-differentiation and absence of non-parenchymal cells. Multicellular hepatic spheroids (MHS) offer a promising alternative, but transporter concentrations, functionality, and suitability for hepatobiliary transport studies remain unclear. We evaluated an all-human MHS model, comprised of transporter-certified™ cryopreserved primary human hepatocytes (PHH), Kupffer, stellate, and endothelial cells, for long-term hepatic transporter assessment. Over Cellular and molecular life sciences : CMLSEvaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.PMC12804587R35 GM122576P30 CA016086S10 OD032350P30 ES010126HDTRA1-19-1-0013P42 ES031007S10 RR024595Bishop CEFallon JKWan MMurphy WABrouwer KLRHartauer MHo HTiley JBfalseEvaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.There is growing demand for improved in vitro liver models to better predict in vivo pharmacology, specifically drug disposition mediated by hepatic transporters and assessment of transporter-mediated drug interaction risk. While 2D sandwich-cultured human hepatocytes (SCHH) remain valuable, they are limited to short-term use due to hepatocyte de-differentiation and absence of non-parenchymal cells. Multicellular hepatic spheroids (MHS) offer a promising alternative, but transporter concentrations, functionality, and suitability for hepatobiliary transport studies remain unclear. We evaluated an all-human MHS model, comprised of transporter-certified™ cryopreserved primary human hepatocytes (PHH), Kupffer, stellate, and endothelial cells, for long-term hepatic transporter assessment. Over 2025-01-01T00:00:00Z2025 Dec2026-06-13T04:49:12.609Z2026-06-13T03:09:10.059ZS-EPMC128045874146794510.1007/s00018-025-05996-z