Developing clinical-grade intestinal organoids for regenerative medicine applications

New culture system enables the stable, scalable, and low-cost production of clinical-grade intestinal organoids, as reported by researchers from Science Tokyo. Whereas conventional organoid cultures rely on materials and substances unsuitable for clinical use, this innovative strategy uses clinical-grade collagen and good manufacturing practice-compliant reagents/factors and techniques to achieve drastically enhanced growth. The results put us one step closer to organoid-based regenerative therapies for conditions like inflammatory bowel disease.

Inflammatory bowel disease (IBD) and other intestinal disorders affect millions of people worldwide, often causing lasting damage to the lining of the gut. In severe cases, this damage can become irreversible, leaving surgery as one of the few remaining treatment options. In recent years, however, regenerative medicine has emerged as a promising alternative approach, raising the possibility that damaged tissues could one day be repaired using a patient’s own cells. Central to this vision are tiny three-dimensional replicas of human organs known as ‘organoids,’ which are grown from stem cells and can mimic important features of real tissues.

Despite their potential, intestinal organoids have largely remained confined to research laboratories. A major challenge in the field is that conventional organoid cultures rely on materials that are not suitable for clinical use in humans. Another problem involves WNT3A, a protein essential for culturing intestinal stem cells, but one that is expensive and chemically unstable. These issues make it difficult to reliably produce the large numbers of cells needed for organoid-based regenerative therapies, creating a gap between experimental research and practical medical applications.

Against this backdrop, a research team led by Junior Assistant Professor Tomohiro Mizutani, graduate student Hady Yuki Sugihara, and Professor Ryuichi Okamoto from the Department of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo), Japan, in collaboration with Professor Mamoru Watanabe from the Graduate School of Medicine, Juntendo University, Japan, has developed a potential solution to these challenges. In their latest study, published in Volume 17 of the journal Stem Cell Research & Therapy on March 29, 2026, the researchers established an efficient, low-cost culture system for patient-derived colorectal organoids using materials and methods compatible with good manufacturing practice (GMP) standards.

Using biopsy samples collected from 60 patients, including individuals with IBD, the researchers successfully established organoid cultures in more than 80% of cases. Instead of relying on Matrigel—a commonly used animal-derived material unsuitable for clinical applications—they grew organoids in Type-I collagen, which is a clinical-grade alternative. The team also introduced several methods to improve scalability, including automated area-based measurements to estimate cell numbers and a large-format culture system capable of producing tens of millions of cells efficiently.

The research team hypothesized that stabilization of Wnt signaling would be necessary to improve the success rate of human intestinal organoid culture. A key feature of the proposed system was the replacement of WNT3A with a synthetic peptide called PG-008, which activates the same signaling pathway. Cultures grown with this peptide showed dramatically enhanced growth compared to those grown using WNT3A. Single-cell RNA sequencing revealed that PG-008 strongly enriched intestinal stem cell populations within the organoids, which are essential for tissue regeneration. “The enhanced proliferative capacity unlocked by our approach enabled us to efficiently produce stable colorectal epithelial organoid cultures from a wide variety of patient-derived samples,” highlights Sugihara.

Taken together, the results point toward a scalable, cost-effective path for producing patient-derived intestinal organoids for use in clinical settings. “Our findings represent a major step forward in the development of regenerative medicine based on organoid transplantation for intestinal conditions, such as IBD,” concludes Mizutani. Beyond therapeutics, the proposed platform also offers a powerful tool for studying how the gut repairs itself after injury, a process that is still not fully understood.

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About Institute of Science Tokyo (Science Tokyo)

Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”