Peter van Mourik

124 Chapter 5 Overall, 477 organoid cultures were successfully isolated from 502 biopsy procedure (success rate of 95 %). One biopsy sample was lost during shipment due to incorrect storage temperature. A number of samples failed to generate organoids for different reasons. First, several samples were of insufficient viability (16 samples, 3.2 %). Secondly, a number of samples were contaminated during the biopsy procedure (7, 1.4 %) or in the organoid laboratory (1, 0.2 %). The success rate of forceps biopsy procedures was 93.6 %, in comparison to 96.4 % for rectal suction biopsies (Table 1). The majority of samples were processed in the laboratory within 48 hours after the biopsy procedure, while 17 of the 502 samples were processed between 48 and 72 hours after collection, of which 1 failed due to insufficient viability. DISCUSSION In our study including 502 subjects from 13 countries and 33 different hospitals, low biopsy complication rates and high success rates of organoid generation were achieved, underscoring the feasibility of international cohort studies using intestinal organoids. Organoids studies have demonstrated great potential to change the way drugs are developed and clinicals trials can be performed. It has opened up new avenues for personalized medicine and patient stratification in clinical trials 1,2,8 . The novelty of the technology and the requirement of specialized personnel have prompted us to investigate models of organoid application. Here we introduce an international collaboration using a centralized laboratory to implement personalized organoid cultures, which can be particularly relevant in rare diseases with large genetic variability such as Cystic Fibrosis. Our study shows that it is feasible to set up international studies and generate data on a large group of rare patients in centralized labs. The methods used in this study could be implemented for other diseases and efficient shipment of tissue material across countries demonstrates the feasibility of this personalized patient stratification approach for clinical trials, predictive diagnostic tests, and generation of biobanks comprised of internationally obtained samples. Our study finds very low rates of serious adverse events (<1 % ) for both forceps biopsy and rectal suction biopsy, comparable to previous studies 11,12 . These data implicate that both rectal suction biopsies and forceps biopsies are effective tools for obtaining intestinal adult stem cells. Rectal suction biopsy is commonly used by pediatric gastroenterologists to diagnose Hirschsprung, and can be safely performed in newborns 12 . In contrast, rectal suction biopsies are rarely indicated in the adult population which limits the experience of adult gastroenterologists with