COLON STEM CELLS ASSOCIATED WITH COLITISAND COLORECTAL CANCER AND METHODS OF USE

摘要

The disclosure provides methods of isolating and propagating self-renewing colonic stem/progenitor cells (CS/PCs) that express aldehyde dehydrogenase (ALDH1), from colon cancer and colitis tissues, as well as from normal colon tissue, methods of identifying agents for modulating the proliferative status of such cells, an methods of screening patients having colitis for an increased risk of colorectal cancer. Novel methods of adherent cell culture propagation of CS/PC involving use of colon-specific fibroblastic stromal cells (CFSt) {i.e. the “niche” cells) as support cells (e.g., “feeder cells”). The present disclosure encompasses an isolated mammalian pluripotent colon epithelial stem/progenitor cell (CS/PC), or a population of said cells, where each CS/PC may comprise a detectable marker, where the detectable marker is aldehyde dehydrogenase 1 (ALDH1), and where the isolated population of mammalian pluripotent CS/PCs is substantially free of cells that do not have the detectable ALDH 1 marker. The disclosure encompasses further provides methods for determining the prognosis for a patient for developing a colon cancer, the method detecting the presence of at least one marker in a tissue section from a patient, the marker or plurality of markers indicating the presence of a pluripotent colon epithelial stem/progenitor cells and indicating the prognosis of the patient for developing a colon cancer.