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1. (WO2018204913) INFLAMMATORY BOWEL DISEASE STEM CELLS, AGENTS WHICH TARGET IBD STEM CELLS, AND USES RELATED THERETO

Pub. No.:    WO/2018/204913    International Application No.:    PCT/US2018/031370
Publication Date: Fri Nov 09 00:59:59 CET 2018 International Filing Date: Tue May 08 01:59:59 CEST 2018
IPC: A61K 35/38
C12N 5/07
A61K 38/18
A61P 1/00
Applicants: TRACT PHARMACEUTICALS, INC.
BOARD OF REGENTS OF THE UNIVERSITY OF HOUSTON SYSTEM
Inventors: XIAN, Wa
MCKEON, Frank
VINCENT, Matthew P.
Title: INFLAMMATORY BOWEL DISEASE STEM CELLS, AGENTS WHICH TARGET IBD STEM CELLS, AND USES RELATED THERETO
Abstract:
The present invention addresses IBD from the standpoint of mucosal stem cells cloned from defined regions of the gastrointestinal tract. In the case of pediatric Crohn's disease, for example, isolation of those stem cells according to the methods of the present invention reveals a pattern of inflammatory gene expression in stem cells from the terminal ileum and colon that is epigenetically maintained despite months of continuous cultivation in the absence of immune or stromal cells, or of intestinal microbes. Superimposed on this distributed inflammatory phenotype is a differentiation defect that profoundly and specifically alters the mucosal barrier properties of the terminal ileum. The co-existence of diseased and normal stem cells within the same endoscopic biopsies of Crohn's disease patients implicates an epigenetically enforced heterogeneity among mucosal stem cells in the dynamics of this condition.