Peter van Mourik

191 General discussion Moreover, one could even imagine a scenario when e.g. the corrector from company X in combination with a potentiator from company Y would be superior to established combinations. In order to efficiently use organoids for individualized therapeutic development, one first needs to generate and successfully culture the organoids and create universal access to these tissues. Once the tissue is widely available for research and clinical purposes, concerted international efforts could ensure that all (new) variants are studied and therapies are developed. Currently available biobanks are a first step towards that goal, but improvements could be made to further boost individualized medicine in CF. THE ORGANOID BIOBANK AS AN INFINITE AND ACCES- SIBLE RESOURCE FOR CF CLINICAL CARE AND RE- SEARCH Intestinal organoids are obtained by isolating stem cells from rectal tissue, which can be safely and easily obtained through either forceps or rectal suction biopsy (chapter 5) 68,69 . Moreover, generating a large international biobank of organoids is feasible, which creates the opportunity to collect organoids with very rare mutations. Of the more than 2000 reported mutations, only 432 have been annotated, which leaves more than 1500 variants that have not been characterized (genet.sickkids.org , www.cftr2.org ). These variants are extremely rare and sometimes unique for a single person or family, which complicates research into the pathogenicity and creates uncertainty for both the individual and the caregiver 52,70 . Furthermore, people with these variants are currently excluded from CFTR-modulator treatment since therapy is restricted to certain well-studied mutations included in the drug label 71,72 . In chapter 5 , we show that with well-defined protocols, organoids can be generated from these individuals even if they live in a remote area and the cells thus have to travel long distances over extended periods. Outside of studies run in hospitals, determined individual patients have even managed to include their own organoids in the biobank by arranging biopsies and transport themselves 73 . Cystic Fibrosis organoids can be expanded, cultured and stored for prolonged periods while maintaining the CF phenotype 66 , which enables the generation of a living biobank with (almost) infinite material for research purposes. Currently, a collaboration between Hubrecht Organoid Technology and the University Medical Centre Utrecht has resulted in a combined biobank of 664 CF organoid samples with 9