Adverse drug reactions remain a notable challenge in healthcare, responsible for a substantial number of hospitalizations and deaths each year. Now, researchers are reporting a breakthrough in predicting how individuals will respond to medications: lab-grown, miniature human livers. A collaboration between Cincinnati Children’s Hospital Medical Center and Roche has yielded a new platform utilizing thes “liver organoids” to model patient-specific drug responses, possibly paving the way for more effective personalized medicine and safer drug advancement [[1]].
Scientists have developed miniature, lab-grown human livers capable of predicting toxic reactions to medications, offering a potential leap forward in personalized medicine and drug safety.
Researchers at Cincinnati Children’s Hospital Medical Center, in collaboration with pharmaceutical company Roche, have created an advanced platform using these “liver organoids” to estimate which drugs might trigger harmful immune responses in certain individuals. This innovation addresses a critical need in healthcare – anticipating how patients will react to medications *before* they are administered.
The system, built entirely from human cells, combines stem cells derived from patients with their own immune cells. This combination accurately replicates how a person’s genetic makeup influences their body’s reaction to drugs. Researchers can now model individual responses with greater precision than previously possible.
The team demonstrated the platform’s capabilities by recreating liver damage caused by the antibiotic flucloxacillin, a reaction that only occurs in people carrying the HLA-B*57:01 genetic variant. This successful replication validates the model’s ability to pinpoint genetically-linked drug sensitivities.
Using the model, scientists can observe the activation of T cells (a type of immune cell), the release of cytokines, and the resulting damage to liver cells – processes that mirror what happens in susceptible patients. This detailed view of the immune response is crucial for understanding adverse drug reactions.
“We wanted to create a human system that captures the interaction between the liver and the immune system,” explained Dr. Fadoua El Abdellaoui Soussi, a co-author of the study. “Now we can understand why certain medications cause liver injury in only a small subset of individuals.”
The authors describe the new model as “an important step toward a patient-relevant, laboratory-reproduced human biology.” This advancement could significantly reduce the risk of adverse drug reactions and accelerate the development of safer, more effective treatments.
The liver organoids were generated from induced pluripotent stem cells (iPSCs), reprogrammed cells capable of becoming any type of tissue. These were combined with CD8⁺ T cells from each donor, resulting in a biological model constructed entirely from human cells that can reproduce real-world immune responses. This approach overcomes the limitations of traditional lab models and animal testing, which often fail to capture the genetic and immune diversity of humans.
This work builds upon previous research by Dr. Takanori Takebe, a pioneer in generating human liver organoids. By refining these methods into a miniaturized platform – allowing for the simultaneous growth of numerous liver organoids under strict control – the CuSTOM Accelerator team at Cincinnati Children’s has transformed a laboratory discovery into a practical and efficient tool for precision drug toxicity testing.
Cincinnati Children’s is a global leader in organoid-based human medicine, having developed the first functional human intestinal structures in 2010. Under the direction of Dr. Magdalena Kasendra, the CuSTOM Accelerator program collaborates with the biopharmaceutical and technology industries to translate these discoveries into concrete solutions for personalized medicine and drug safety testing.
Researchers plan to further automate testing on the organoids and apply them to samples from individuals with diverse genetic profiles, observing how each organism reacts to various medications. This next step could enable early detection of adverse reactions and the development of safer treatments for patients.
The study was recently published in the journal Advanced Science.
Photo article: Models of human liver organoids cultivated with autologous CD8 T cells (marked in green). These tissues can be used during the drug development process to observe liver toxicity, according to a new study published by experts at Cincinnati Children’s. Credit: Cincinnati Children’s.
