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A living organoid biobank of patients with Crohn's disease reveals molecular subtypes for personalized therapeutics.
Tindle, Courtney; Fonseca, Ayden G; Taheri, Sahar; Katkar, Gajanan D; Lee, Jasper; Maity, Priti; Sayed, Ibrahim M; Ibeawuchi, Stella-Rita; Vidales, Eleadah; Pranadinata, Rama F; Fuller, Mackenzie; Stec, Dominik L; Anandachar, Mahitha Shree; Perry, Kevin; Le, Helen N; Ear, Jason; Boland, Brigid S; Sandborn, William J; Sahoo, Debashis; Das, Soumita; Ghosh, Pradipta.
Afiliação
  • Tindle C; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Fonseca AG; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Taheri S; Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Katkar GD; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Lee J; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Maity P; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Sayed IM; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ibeawuchi SR; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Vidales E; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Pranadinata RF; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Fuller M; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Stec DL; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Anandachar MS; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
  • Perry K; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA.
  • Le HN; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ear J; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Boland BS; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: bboland@health.ucsd.edu.
  • Sandborn WJ; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: wsandborn@health.ucsd.edu.
  • Sahoo D; Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: dsahoo@ucsd.edu.
  • Das S; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: soumita_das@uml.edu.
  • Ghosh P; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; HUMANOID™ Center of Research Excellence (CoRE), University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 9
Cell Rep Med ; : 101748, 2024 Sep 20.
Article em En | MEDLINE | ID: mdl-39332415
ABSTRACT
Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create 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 modeling the colonic epithelium in active disease and identified two major molecular subtypes immune-deficient infectious CD (IDICD) and stress and senescence-induced fibrostenotic CD (S2FCD). 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos