New human liver organoid platform offers breakthrough for predicting immune-mediated drug toxicity

CINCINNATI—Researchers at Cincinnati Children’s Hospital Medical Center in collaboration with Roche, have developed a next-generation human liver organoid microarray platform that that could help predict which drugs may cause harmful immune reactions in some people.  

The study published online Sept. 26, 2025, in the journal Advanced Science describes a miniaturized, fully human liver system built from stem cells and a patient’s own immune cells—a powerful new tool to uncover why some people experience serious, immune-related liver injuries from otherwise safe medications. The study’s co-first author, Fadoua El Abdellaoui Soussi, PhD, and corresponding author, Magdalena Kasendra, PhD, are members of the Center for Stem Cell and Organoid Medicine (CuSTOM) at Cincinnati Children’s.

“Our goal was to create a human system that captures how the liver and immune system interact in patients,” El Abdellaoui Soussi says. “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.”

A human model of immune-driven liver injury

Some drugs that pass early safety testing can still cause idiosyncratic drug-induced liver injury (iDILI)—a rare immune reaction that can lead to severe illness or even drug withdrawal. Standard lab tests and animal models cannot reproduce these complex, patient-specific immune mechanisms.

The newly developed platform bridges this gap by combining induced pluripotent stem cell (iPSC)-derived liver organoids with each donor’s autologous CD8⁺ T cells—the immune cells responsible for attacking infected or damaged tissue. Together, they form a fully human, immune-competent model that mirrors the genetic and immune diversity of real patients.

As a proof-of-concept, the research team recreated liver injury triggered by the antibiotic flucloxacillin, which occurs only in carriers of the HLA-B*57:01 risk gene. The model reproduced hallmark signs of immune-mediated liver toxicity—including T cell activation, cytokine secretion, and hepatocyte damage—closely matching what occurs in susceptible patients.

“Our goal has always been to bring human biology into the lab in a way that’s scalable, reproducible, and meaningful for patients,” says Kasendra, who serves as director of research and development at CuSTOM. “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.”

Scaling up research innovation

The platform builds upon foundational work led by study co-author Takanori Takebe, MD, PhD, whose lab pioneered reliable methods for generating human liver organoids from iPSCs. By adapting these techniques into a matrix-free microarray format and integrating patient-matched immune cells, the CuSTOM Accelerator team at Cincinnati Children’s transformed a research innovation into a scalable, precision toxicology system.

The project also showcases a strong collaboration with Roche, whose expertise in translational toxicology was pivotal to the study’s success.

“This partnership shows the power of combining academic innovation with industry experience,” says Adrian Roth, PhD, principal scientific director of Personalized Healthcare Safety at Roche. “Together we’re building predictive human models that can improve patient safety and accelerate the development of new medicines.”

A growing ecosystem for organoid medicine

Cincinnati Children’s has been a global leader in organoid medicine since 2010, when its scientists created the first functional human intestinal organoids.

Under Kasendra’s leadership, the CuSTOM Accelerator partners with biopharma and technology companies to translate these scientific advances into real-world solutions for drug safety, precision medicine, and regenerative therapy.

What’s next

The CuSTOM Accelerator team continues working to automate organoid assays and enable high-throughput screening across large, genetically diverse donor populations. This next phase will allow researchers to capture the full spectrum of human variability - an essential step toward developing therapies that are more effective, inclusive, and personalized.  

Learn more about CuSTOM’s ongoing collaboration with Molecular Devices and Danaher: Collaboration to Develop Liver Organoids for Drug Toxicity Screening - Research Horizons

“This work reflects the vision of CuSTOM—to turn human organoid science into practical tools that improve health,” Kasendra says, “This is just the beginning - by bridging biology, engineering, and clinical insight, we’re getting closer to predicting how real patients will respond to new treatments before they ever reach the clinic.”

About the study

Cincinnati Children’s and University of Cincinnati co-authors included co-first author Michael Brusilovsky, PhD, (now with Sanofi), Emma Buck, MS, (now at Imanis Life Sciences), W. Clark Bacon, MS,  Sina Dadgar, PhD, Riccardo Barrile, PhD, and Michael Helmrath, MD. Collaborators also included experts from Genentech, Inc., and Molecular Devices LLC.

Funding sources for this research include Roche, Danaher, and the Farmer Family Foundation.