Translating Organoid technology towards a Clinical Application

Liver disease is a major global health problem, affecting millions of people worldwide and causing over two million deaths annually. Liver transplantation remains the only curative treatment, yet the severe shortage of donor organs means that only one in ten patients receives a transplant. The TOCA project, a collaboration between Utrecht University and Scinus Cell Expansion BV, was established to develop an innovative, cell-based alternative by growing patient-derived liver cells in a bioreactor system. This public-private partnership has made significant progress in scalable liver cell expansion, bringing regenerative liver therapy closer to clinical application. 

Beyond its impact on patients, liver disease places a heavy financial burden on healthcare systems due to prolonged hospital stays, high treatment costs, and lifelong immunosuppressive therapy. As the prevalence of liver disease continues to rise, the demand for new treatment options becomes more urgent. The TOCA project addresses this global medical and economic challenge by developing a cell therapy approach that could reduce the need for donor organs, lower healthcare costs, and increase the number of transplantable livers through the regeneration of damaged bile ducts. 

To achieve this, TOCA developed a closed-loop bioreactor system that enables the large-scale production of liver cells from a patient’s own tissue. This method ensures high cell yields while maintaining hepatic functionality, including albumin secretion and enzyme activity, proving their suitability for therapeutic applications. 

TOCA successfully implemented standardized operating procedures (SOPs) for organoid expansion and differentiation, ensuring consistent quality, reproducibility, and GMP compliance. The project demonstrated an average cell yield of 189 million per batch, a threefold increase over spinner flask cultures and 63 times higher than static cultures. These validated workflows lay the foundation for further preclinical studies and clinical trials, marking an important step toward a scalable, patient-specific therapy for liver disease.