Figure 1.

Study outline: Creation of a living biobank of adult stem cell-derived PDOs for enhancing personalized therapeutics in CD

Key aspects of a rationalized goal and study motivation are summarized (Step 1). Patients were prospectively enrolled in this study as source of colonic tissue biopsies for the isolation and creation of the CD PDO biobank. Clinical, pathological, and treatment history and the Montreal classification of disease were collected (see Table S1). PDOs were generated from the adult stem cells at the crypt base, expanded, and biobanked (in Step 2) for use in various assays (in Step 3). Various multiomic, morphologic, and functional studies that were performed, some in low- and others in high-throughput modes (HTP; in 96-well plates) for systematic molecular and phenotypic characterization (cataloged in Table S2). The study ends with proof-of-concept therapeutic studies (Step 4) in which drugs are rationalized and paired to each subtype with the intention to specifically reverse driver phenotyped within a subtype without crossover benefits to the other subtype. RCT, randomized controlled trials; OR, odds ratio; CI, confidence interval.