Mini-Guts to the Rescue: Introducing 3-D Organoid Cell Cultures

A cost-effective 3-D organoid biobank provides a versatile translational research tool.

The Scientist Creative Services Team and MilliporeSigma
Jan 19, 2022

In vitro cell culture models are indispensable tools for translational research, but the biological relevance of 2-D cell lines is limited by reduced cell-to-cell interactions compared to original tissue niches. This is especially true for anatomically and physiologically diverse organs such as the gastrointestinal tract, which depends on communication between various cell types to achieve distinct yet coordinated functions along its length. 

Immunocytochemical characterization of human colon organoids (Colon-87, SCC321). Human colon PDOs are positive for colon-specific markers: CA II, CA IV and Mucin5B, posterior hindgut marker: CDX2, stem cell markers: Lgr5 and Sca1 and epithelial markers: TPH-1 and E-Cad.
courtesy of milliporesigma

3-D organoid cell culture models—miniature organs grown from tissue-derived stem cells—are useful alternatives to traditional 2-D systems. Under carefully maintained culture conditions that mimic the stem cell niche, these cells self-organize to form mature organoids that retain the cellular subtypes of the native tissue. 3-D organoids derived from adult human tissue samples provide a more accurate representation of in vivo disease because they preserve the original tissue physiology, molecular pathology, and patient- and disease-specific characteristics. As translational research models, they are a versatile tool for understanding pathobiology, performing preclinical drug screens, and providing personalized treatment.

Despite their advantages, patient-derived organoids require access to human tissue samples, specialized growth and maintenance protocols, meticulous quality control procedures, and a secure, up-to-date repository of patient characteristics. The added cost and burden of growing and maintaining a patient-derived organoid biobank creates an insurmountable hurdle for many researchers who may opt instead to use animal models. However, animal models have their own limitations, particularly for human gastrointestinal disorders that differ anatomically, genetically, and physiologically from their animal counterparts. Moreover, because human gastrointestinal diseases are heterogenous, using animal models to explore a “one size fits all” approach to treatment may be counterproductive.

Human large intestine tissue under a microscope.
iStock

MilliporeSigma provides a cost-effective 3-D gastrointestinal biobank of over 50 well-characterized organoids that adheres to industry quality standards and provides a versatile, easily-accessible translational research tool. Their 3dGRO Gastrointestinal PDO Biobank Organoids are derived from a wide range of normal and diseased adult patient tissue samples, including stomach, small intestine, colon, rectum, ulcerative colitis, irritable bowel syndrome, and cancer, and have been developed using Hubrecht Organoid Technology (HUB). This new biobank eliminates the complexity of patient-derived intestinal organoid use, and when grown in optimized 3dGRO L-WRN Conditioned Media, the organoids maintain their genetic and phenotypic stability over many passages. The organoids also retain donor-specific features such as age, sex, and disease-associated differences, providing researchers with a reliable way to study underlying disease mechanisms, test existing drugs, develop new therapies, and personalize treatment. For example, organoid cultures derived from malignant gastrointestinal tissues retain genetic changes that are unique to the disease, tissue subtype, and individual patient. This is particularly useful for predicting patient responses to various chemotherapeutic agents. Overall, this new gastrointestinal organoid biobank helps researchers overcome the limitations of 2-D cell culture and animal models, maximizes the use of tissue samples collected from routine patient testing, and provides an effective model for translational gastrointestinal research that is anatomically, physiologically, and genetically accurate.