Current understanding concerning intestinal stem cells

Table 1 Bioactive proteins from niche cells maintain the proliferative status in intestinal stem cells

Niche cell	Bioactive protein	Receptor	Target pathway	ISC proliferation	ISC differentiation
Paneth cell	Wnt 3	LRP5/6 and Frizzled	Wnt/β-catenin	↑	/
Paneth cell	Dll1/4	Notch 1/2	Notch	↑	↓
Paneth cell	EGF	EGFR	Ras/Raf/Mek/Erk/MAPK	↑	/
Myofibroblast	R-spondin1	Lgr4/5	Wnt/β-catenin	↑	/
Myofibroblast	Noggin	BMP4	BMP/Smad	/	↓

ISCs: Intestinal stem cells. ↑: Increase; ↓: Decrease; /: No alterations.

Table 2 Debate on intestinal stem cells’ locations and their relevant characteristics

Location	Representative research by	Number per crypt	Sensitivity to IR	Cell-cycle	Cell-division	DNA segregation
CBC	Clevers H’s team	14-16	Less than mature cells	21.5 h	Symmetry	Random
4+ position	Potten CS’s team	4-6	Apoptosis upon receiving 1 cGy	Approximately 24 h	Asymmetry	Hierarchy

CBC: Crypt basement column cells.

Table 3 Characteristics of crypt basement column cells stem cells and reserve intestinal stem cells

ISC type	Main location	Cell-cycle status under intact conditions	Differentiating capability	Foreign stimuli-induced response	Leading pathway	Typical marker genes
CBC stem cell	Crypt basement	Active	Yes	Apoptosis	Wnt/β-catenin	Lgr5
Reserve ISC	4+ position	Slow	Yes	Proliferation	Unknown but independent of Wnt/β-catenin	Bmi1, HopX, Lrig1, mTERT

CBC: Crypt basement column cells; ISC: Intestinal stem cell.

Table 4 Two systems for expanding intestinal stem cells

Established by	Published year	System type	Substrate	Supplemental factor	Medium	Cultured content	Expanding duration of cultured content
Sato et al[23]	2009	3D	Matrigel containing laminin α1 and α2	N2, B27, Wnt3, EGF, Noggin, R-spondin1, Jagged-1 and Y-27632 dihydrochloride	Serum-free	ISCs	Up to 1 yr
Ootani et al[62]	2009	3D	Collagen gel containing collagen I and III	/	Containing 20% of FCS in medium	Small pieces of intestinal tissue	Up to 1 yr

EGF: Epithermal growth factor; ISCs: Intestinal stem cells.