Q&A: Patient-derived organoid model may help tailor treatment for patients with UC
A study published in the Nature Communications concluded that a patient-derived organoid model will provide insights into pathogenesis of ulcerative colitis, which may help tailor care to the individual patient.
Healio Gastroenterology spoke with Emina Huang, MD, from the departments of colorectal surgery and cancer biology, Cleveland Clinic, Lerner Research Institute and Digestive Disease & Surgery Institute, to discuss the study results and how the research can be translated into patient care.
Healio: Can you briefly discuss the study?
Huang: So one of the gaps in the field is that we don’t have any patient-derived models for inflammatory bowel disease, particularly for UC that include both the epithelium and the surrounding neighborhood or stroma, and so this was an effort to create such a model from individual patients.
Healio: How can we translate this research into patient care?
Huang: We were looking at both the epithelium and the surrounding stroma, andin this study, we were able to challenge the organoid with a drug that we thought could modulate how the cells looked and behaved to be more normal, so we already went ahead and have tested at least one agent that might be used in this context and found it to be effective in this model.
Healio: What is the take-home message of the study?
Huang: The take-home message of the study is that for the first time, we have a patient-derived model of a form of IBD called UC that mimicked the primary tissue and can be perpetuated indefinitely in vitro, so in a test tube, or in a preclinical model and retain the characteristics of the parental tissues. These organoids can then be challenged with different types of chemotherapy or genetic alterations to see what type of therapy might be possible to prevent the disease from occurring or prevent the downstream sequelae of the disease.
Healio: What is the next step in your research?
Huang: So depending on which direction we want to study, we can use this model to study the disease, whether it’s looking at abnormal regeneration, gut development or maybe understanding the disease more thoroughly so pathogenesis, or two long-term sequelae of this disease are fibrosis or scarring or even the development of cancer. So depending on what direction we want to take this, we can use these models as individual avatars for patients and look at the manipulation of genes by using genetic manipulation or drugs to try to modify the phenotype of these organoids to be more normal. That this is the first time that we’ve been able to create from human tissues a model containing both the epithelium and the stroma, so we can view the neighborhood as well as the major players, and use the organoids to predict, for example, response to drugs.