Peter van Mourik

121 Centralized intestinal organoid generation INTRODUCTION Intestinal cell cultures derived from adult stem cells (organoids) are increasingly used to study organ development and diseases such as cancer, inflammatory conditions and inherited diseases 1–5 . Organoids can be expanded almost indefinitely, and maintain functional characteristics of their parental organ 1,6,7 . The genetic stability and long-term expansion allow the generation of organoid collections in biobanks. Initial studies in Cystic Fibrosis patients 8 demonstrated the direct correlation of the in vitro response of organoids and the clinical response of the same patient to drug treatment. Therefore, we have set up an international effort to determine the use of organoid based personalized in vitro drug testing in individual patients for Cystic Fibrosis. In the international HIT-CF organoid study, rectal biopsies are collected from Cystic Fibrosis patients with ultra-rare genetic mutations. The organoids are tested with a number of clinical phase compounds in central labs 9,10 . The tests will stratify patients for specific clinical drug trials based on the in vitro response. Intestinal adult stem cells can be harvested from the rectum through forceps or suction biopsy procedures, which are commonly used for other clinical indications and are generally considered safe 11,12 . Nevertheless, the risks of these biopsy procedures and the success rate for generating viable organoid cultures are unknown. In addition, we want to investigate other logistic and technical steps in the organoids generation process that impact the success. Previously, we identified a number of potential challenges such as the number of biopsies, the quality of the biopsies (i.e. viability and presence of stem cells in the obtained tissue), and the transportation time to the specialized organoid generation lab. These factors could impact the success rates of organoid establishment. We here report on the safety of both forceps- and rectal suction biopsies, the feasibility of international transport of biopsies and the success rate of organoid establishment in the European HIT-CF Organoid Study in adults with Cystic Fibrosis 10 . METHODS Adult patients with Cystic Fibrosis were included in 33 hospitals in 12 European countries for the HIT-CF Organoid Study (NTR7520). This study and the accompanying informed consent form were approved by independent ethics committees at each participating site. Written informed consent (and assent, if appropriate) was obtained from each patient and/or the patient’s legal guardian. 5