The intestinal epithelial stem cell: the mucosal governor

Abstract

Summary. All epithelial cells in the small and large intestine are thought to originate from stem cells located towards the base of the crypts of Lieberkü hn. To-date, there are no specific intestinal stem cell markers, hence stem cell properties can only be inferred. A range of experimental techniques have been employed including cell position mapping, radiation regeneration (clonogenic) assays, chimeric and transgenic mice. This review discusses the implications of experiments performed using these techniques in order to deduce the number, location and functional properties of stem cells. Stem cell homeostasis is maintained by cell proliferation and death 'through apoptosis'. The various growth and matrix factors and genes which may control these processes, and be important for stem cell function, are discussed along with their carcinogenic and clinical implications.Keywords: stem cell, intestine, apoptosis, epithelium Proliferative organization of the intestinal epitheliumThe lumenal surface of the intestine is lined by a simple columnar epithelium. The surface of both the small and large intestine is folded into a number of deep cavities or crypts of Lieberkü hn, which are embedded in connective tissue. In the small intestine the surface area is further increased by finger-like projections, or villi, also covered by epithelium, which protrude into the gut lumen. Although the crypts are approximately 10 × smaller than the villi, they are much more numerous (7 × more in the duodenum, 4 × more in the ileum, Wright & Alison 1984). The effect of these numerous 'pits and projections' is to form a huge surface area. This surface area is further expanded by the presence of a carpet-like covering of microvilli on the apical (lumenal) surface of the columnar epithelial cells.The functional cells of the epithelium are located predominantly towards the lumenal pole of the cryptvillus axis (i.e. on the villi of the small intestine and at the top of the crypts of the large intestine). Once they have fulfilled their differentiated function (brush border enzyme secretion, mucus secretion, nutrient and water absorption) the cells senesce and are sloughed off into the lumen itself, possibly after initiating some aspects of the Int.

Damage-induced apoptosis in intestinal epithelia from bcl-2-null and bax-null mice: investigations of the mechanistic determinants of epithelial apoptosis in vivo

“…It was also possible that pharmacokinetic di erences for drug delivery might occur in the null compared to the wild-type animals; radiation avoids such potential problems. Figure 3 shows the apoptotic response of intestinal crypts 4.5 h (the peak timepoint) following 1 Gy Figure 1 Examples of mitotic cell (arrow) and apoptotic cells (arrowheads) in midcolonic crypts of (A) bcl-2 wild-type and (B) homozygously bcl-2-null mice 4.5 h after 40 mg/kg 5FU (staining of 3 mm para n sections, haematoxylin and eosin stained, 61000, as described previously in Merritt et al, 1996) (which virtually saturates the apoptotic response of small intestine) or 8 Gy (which saturates the apoptotic response of colon) of g-radiation (Potten, 1990;Potten et al, 1997;Potten and Grant, 1998). Again, after additional statistical analysis using a Student's t-test, no major di erences were observed in the apoptotic yield of bax-null mice after 4.5 h (Table 1).…”

The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine

“…Various considerations, observations and mathematical modelling studies suggest that the stem cells of the small intestinal crypt are distributed in the cell positions immediately above the Paneth cells (see Paulus et al 1992; Qiu et al 1994;Potten et al 1997), which on average would be the fourth cell position. The present data confirm earlier observations (Potten, 1977(Potten, , 1995 that the greatest number of spontaneous apoptotic events are observed in this region (at 3-5 cell positions from the bottom of the crypt).…”

“…with the levels of damage induced , and these observations have been interpreted to suggest that the crypt may contain two tiers of clonogenic cells, as well as the ultimate steady-state stem cells. which are easily killed and die by apoptosis following small doses Potten et al, 1997).…”

Regulation of adult intestinal epithelial stem cell development by thyroid hormone during Xenopus laevis metamorphosis

“…Their descendants actively proliferate and then, as they migrate along the crypt-villus axis, gradually differentiate into major absorptive cells, goblet cells, enteroendocrine cells, and Paneth cells (Cheng and Leblond, 1974;Bjerknes and Cheng, 1981). It is generally known that the microenvironment around the stem cells known as the "niche" plays key roles in this epithelial cell-renewal (Potten et al, 1997;Mills and Gordon, 2001). Recently, several types of cells including subepithelial myofibroblasts (Powell et al, 1999), endothelial cells (Paris et al, 2001), intraepithelial lymphocytes (Komano et al, 1995), and enteric neurons (Bjerknes and Cheng, 2001) have been proposed as "niche players," which affect the stem cells and their descendants.…”