Learning by doing

How many students can claim that they’ve handled diseased cells, made patient-derived organoids and tested a hypothesis – in real-time? Within the framework of the Utrecht Platform for Organoid Technology, we’re offering the first Utrecht Summer School course on organoids: Human Intestinal Organoids and Application in Cystic Fibrosis, which will give up to 12 lucky, motivated students a hands-on experience of a lifetime.

Cystic fibrosis is complex, fatal and has no cure

Cystic fibrosis is an inherited genetic disorder that is fatal and incurable. It mainly affects the lungs, but also damages the digestive system and other organs in the body. It’s caused by any one or combination of almost 2,000 possible mutations in the CTFR gene, which makes designing specific treatments difficult. Sadly, many mutations are rare, leaving patients ineligible for clinical trials, and even if patients have the same mutation and receive the same treatment, they may respond differently.

A quick and robust prediction test

The CTFR gene is responsible for the movement of ions and water into and out of cells. When mutated, it loses its ability to function properly, resulting in the production of abnormally thick sticky mucus. My group developed a personalized organoid assay that can predict a patient’s response to a drug treatment. Organoids are 3D mini organs that carry the same genetic information as the patient and allow us to study the cellular behavior of the patient’s tissue in the lab. The assay is based on the physical swelling capability of patient-derived organoids and is sensitive enough to distinguish individual patient responses, even when they have the same mutation. We’ve patented this assay and are working to implement this as a cost-effective, quick method to determine drug responses in individual patients.

The Utrecht Platform for Organoid Technology centralizes our knowledge and expertise and together, we have the opportunity to share and implement this Utrecht-based technology around the world

Summer school course

The Utrecht Summer School course is a mixture of classroom theory, discussion and practical bench work. Topics include the devastation of cystic fibrosis, the science behind its genetics, the development of organoids and the ethics surrounding this topic, such as informed consent and anonymization.

Students will generate organoids from biobanked tissues from patients with cystic fibrosis in order to test how the organoids will respond to two different therapies. These particular patient tissues have a rare or ultra-rare mutation and students will conduct a literature analysis before formulating a hypothesis. After conducting their experiments, students will learn how to validate and perform quality control assessments. We’ve designed this course with the highest scientific standards, to show students the potential societal impact and to expose them to the rigor of academic training.  

Organoids are a powerful tool

Cystic fibrosis is one example of how we’re using organoids, and because the swelling assay produces fast results, it’s a great for our summer school course. Other groups on campus use organoids to understand human development and disease processes; to develop new therapies that target other cancer pathways; to investigate disease mechanisms of diseases in other organs such as the liver and kidney.

Within the scope of the Utrecht Platform for Organoid Technology, a new clinical trial coordinated by Jeanine Roodhart, MD, PhD at the UMC Utrecht was initiated to test the full potential of organoids as a therapy prediction tool. Organoids derived from patients with metastatic colorectal cancer will be generated in order to test and validate whether they can predict each patient’s response to chemotherapy. The trial will also test combinations of therapy on the organoids to determine whether they can improve the future design of better cancer therapies.

U-PORT focusing on training our future generations

The Utrecht Platform for Organoid Technology centralizes our knowledge and expertise and together, we have the opportunity to share and implement this Utrecht-based technology around the world. Setting up a campus-wide framework for logistics, protocols and ethical consideration will enhance our development of great translational models as well as increase our visibility. More importantly, the U-PORT hub will integrate this framework into education and training such that our future leaders truly understand the meaning of for the benefit of the patient.

Jeffrey Beekman, PhD
Nephrology and Hypertension
UMC Utrecht