Stem and progenitor cells of the gastrointestinal tract: applications for tissue engineering the intestine

Abstract The intestinal epithelium is one of the most rapidly cycling tissues in the mammalian body, with the majority of its cells turning over every 4–8 days. Lineage-tracing studies have identified two distinct populations of intestinal stem cells (ISCs): the rapidly dividing crypt base columnar cells marked by Lgr5, and a loosely defined quiescent population of cells at the +4 cell position. In addition, recent studies indicate that both proliferative progenitors and theoretically terminally differentiated cells can “revert” to an ISC phenotype following depletion of the Lgr5+ population. The stem cell niche is maintained by a complex network of signaling molecules, including Wnt, Notch, epidermal growth factor, BMP, and Hedgehog. Gradients of these and other growth factors maintain homeostasis and assist in injury response. Understanding and leveraging these complex processes may further be the goal of creating tissue-engineered intestine (TEI) as a clinical therapy. TEI has been generated from multiple sources of stem/progenitor cells and demonstrated to contain all mature epithelial cell types, associated mesenchymal cells, and to recapitulate the digestive and absorptive capacity of the mature intestine.