A living organoid biobank of patients with Crohn’s disease for personalized therapeutics
October 2024
University of California, La Jolla, USA
Crohn’s disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, the researchers explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. In this study, the researchers created a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modelling the colonic epithelium in active disease and identified two major molecular subtypes. Each subtype shows internal consistency in the transcriptome, genome, and phenome. The spectrum of morphometric, phenotypic, and functional changes within the “living biobank” reveals distinct differences between the molecular subtypes. Drug screens reverse subtype-specific phenotypes, suggesting phenotyped-genotyped CD PDOs can bridge basic biology and patient trials by enabling preclinical phase “0” human trials for personalized therapeutics.
A living organoid biobank of patients with Crohn’s disease reveals molecular subtypes for personalized therapeutics
Debashis Sahoo, William J. Sandborn, Pradipta Ghosh, Brigid S. Boland, Soumita Das
Added on: 12-03-2024
[1] https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00478-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379124004786%3Fshowall%3Dtrue[2] https://www.drugtargetreview.com/news/153450/crohns-disease-discovery-of-two-distinct-molecular-subtypes
