Physiological and pathological role of local and immigrating colonic stem cells

Table 1 Summary of the characteristics of the different types of stem cells in the human colon

	Crypt epithelial stem cells	Subepithelial (pericryptal) myofibroblasts-local stem cell niche	BM-MSCs
Origin	Pericryptal myofibroblasts	Subepithelial CD34+ fibroblasts, perivascular smooth muscle cells, adipocytes, endothelial- and epithelial cells (via EMT), BM-MSCs	Bone marrow
Daughter cells	Enterocytes, goblet cells, endocrine cells, paneth cells	Follicular dendritic cells, crypt epithelial stem cells, pericytes	Subepithelial myofibroblasts, fibrocytes, pericytes, adipocytes, crypt epithelial stem cells
Main regulator pathways of differentiation and/or homing	Wnt/β-catenin, Lgr-5, integrins, growth factor receptors (EGFR, HGFR, I1GFR)	TGF-β1, cytokines (IL-1, -6, -10, TNFα), growth factors (TGFα, GM-CSF, PDGF-AA, -BB, bFGF, KGF, HGF), chemokines (IL-8, MCP1, MIP-1α,-2), inflammatory mediators (PGE2, PAF, PGI2)	Chemokine receptors (CCR-1,-2,-7,-8,-9; CXCR-1,-2,-4,-5,-6), cell adhesion molecules involved in extravasation (VCAM, ICAM, selectins), proinflammatory cytokines (TNFα, IL-8), von Willebrand factor
Physiological function	Epithelial renewal	Growth, repair	Growth, repair, wound healing
Pathological function	Tumorigenesis, ulcer development	Tumorigenesis, cancer progression, inflammation, fibrosis	Tumorigenesis, inflammation, fibrosis
Cell type specific markers	Positive markers: Lgr-5, Musashi-1, CDX-2	Negative markers: smoothelin, caldesmon, desmin	Negative markers: CD13, -14, -45, c-Kit, MHC class I and II
		Positive markers: α-SMA, vimentin, SMM, prolyl 4-hydroxylase, CD90	Positive markers: CD54,-90,-133,-146,-166, Flk-1, Sca-1, stage-specific antigen I, musashi-1, HLA class I
References	1-6, 35, 50	12, 15, 25, 37, 48, 49	8, 9, 11, 20, 26, 29, 35, 37, 41, 58

Lgr-5: Leucine-rich repeat-containing G-protein coupled receptor 5; EGFR: Epithelial growth factor receptor; HGFR: Hepatocyte growth factor receptor; I1GFR: Insulin-like growth factor receptor-1; CDX2: Caudal type homeobox transcription factor 2; EMT: Epithelial-to-mesenchymal transition; TGF: Transforming growth factor; IL: Interleukin; TNF: Tumor necrosis factor; GM-CSF: Granulocyte macrophage colony-stimulating factor; PDGF: Platelet-derived growth factor; bFGF: Basic fibroblast growth factor; KGF: Keratinocyte growth factor; HGF: Hepatocyte growth factor; MCP1: Monocyte chemotactic protein 1; MIP: Macrophage inflammatory protein; PGE2: Prostaglandin E2; PAF: Platelet-activating factor; PGI2: Prostacyclin; SMA: Smooth muscle actin; SMM: Smooth muscle myosin; CCR: Chemokine receptor; CXCR: Chemokine CXC motif receptor; VCAM: Vascular cell adhesion molecule; ICAM: Intercellular cell adhesion molecule; MHC: Major histocompatibility complex; Flk-1: Fetal liver kinase-1; Sca-1: Stem cell antigen-1; HLA: Human leukocyte antigen.