Your browser doesn't support javascript.
loading
Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity.
Sarvestani, Samaneh K; Signs, Steven; Hu, Bo; Yeu, Yunku; Feng, Hao; Ni, Ying; Hill, David R; Fisher, Robert C; Ferrandon, Sylvain; DeHaan, Reece K; Stiene, Jennifer; Cruise, Michael; Hwang, Tae Hyun; Shen, Xiling; Spence, Jason R; Huang, Emina H.
Afiliación
  • Sarvestani SK; Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Signs S; Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Hu B; Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Yeu Y; Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Feng H; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
  • Ni Y; Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Hill DR; Department of Internal Medicine, Gastroenterology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Fisher RC; Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Ferrandon S; Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • DeHaan RK; Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • Stiene J; Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Cruise M; Department of Pathology, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • Hwang TH; Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA.
  • Shen X; Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
  • Spence JR; Department of Internal Medicine, Gastroenterology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Huang EH; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Nat Commun ; 12(1): 262, 2021 01 11.
Article en En | MEDLINE | ID: mdl-33431859
The pathogenesis of ulcerative colitis (UC), a major type of inflammatory bowel disease, remains unknown. No model exists that adequately recapitulates the complexity of clinical UC. Here, we take advantage of induced pluripotent stem cells (iPSCs) to develop an induced human UC-derived organoid (iHUCO) model and compared it with the induced human normal organoid model (iHNO). Notably, iHUCOs recapitulated histological and functional features of primary colitic tissues, including the absence of acidic mucus secretion and aberrant adherens junctions in the epithelial barrier both in vitro and in vivo. We demonstrate that the CXCL8/CXCR1 axis was overexpressed in iHUCO but not in iHNO. As proof-of-principle, we show that inhibition of CXCL8 receptor by the small-molecule non-competitive inhibitor repertaxin attenuated the progression of UC phenotypes in vitro and in vivo. This patient-derived organoid model, containing both epithelial and stromal compartments, will generate new insights into the underlying pathogenesis of UC while offering opportunities to tailor interventions to the individual patient.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colitis Ulcerosa / Organoides Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colitis Ulcerosa / Organoides Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido