Researchers at Cincinnati Children's Hospital Medical Center and Roche have developed a human liver organoid microarray platform that models immune-driven drug reactions. This system, built from patient-derived stem cells and immune cells, accurately replicates toxicities like those from flucloxacillin in genetically susceptible individuals. The findings were published online on September 26, 2025, in Advanced Science.
The new platform addresses a key challenge in drug safety: idiosyncratic drug-induced liver injury (iDILI), where certain medications trigger rare but severe immune responses in specific people despite passing standard tests. Traditional animal and lab models fail to capture these human-specific interactions, but this fully human system combines liver organoids from induced pluripotent stem cells (iPSCs) with the donor's own CD8⁺ T cells to reflect genetic and immune diversity.
As proof of concept, the researchers recreated liver damage from the antibiotic flucloxacillin, which affects only carriers of the HLA-B*57:01 gene. The model showed T cell activation, cytokine release, and liver cell damage, mirroring real patient reactions.
"Our goal was to create a human system that captures how the liver and immune system interact in patients," says co-first author Fadoua El Abdellaoui Soussi, PhD, from the Center for Stem Cell and Organoid Medicine (CuSTOM) at Cincinnati Children's. "By integrating patient-specific genetics and immune responses, we can finally begin to explain why certain drugs cause liver injury in only a small subset of individuals."
The work builds on prior innovations by co-author Takanori Takebe, MD, PhD, who pioneered iPSC-derived liver organoids. Led by corresponding author Magdalena Kasendra, PhD, director of research and development at CuSTOM, the team refined these into a scalable microarray system. Collaboration with Roche enhanced the project's translational potential.
"Our goal has always been to bring human biology into the lab in a way that's scalable, reproducible, and meaningful for patients," Kasendra says. "By linking foundational stem cell science with applied toxicology, this model moves organoid research another step closer to transforming how drugs are developed and tested."
Adrian Roth, PhD, principal scientific director of Personalized Healthcare Safety at Roche, adds: "This partnership shows the power of combining academic innovation with industry experience. Together we're building predictive human models that can improve patient safety and accelerate the development of new medicines."
Cincinnati Children's has led organoid research since 2010, starting with intestinal organoids. The CuSTOM Accelerator now partners with biopharma firms to advance precision medicine. Future efforts focus on automating assays for high-throughput screening across diverse populations.