Table 1.

MSCs in wound healing responses to injury and cancer

		Wound healing response to injury		Wound healing response to Cancer
		Functions	Mechanisms	Functions	Mechanisms
Blood clotting Anti-bacterial		MSCs promote blood clotting MSCs are self-defending by elimination of the invading bacteria	TFs; FVIII Secretion of anti-microbial peptides LL-37, hepcidin, (β-defensin 2 and lipocalin-2 etc.	Not known It is unclear whether the tumor-suppressive effects of MSCs are related to such a self-defending capacity by MSCs
Inflammation	Myeloid cell recruitment	MSCs drive myeloid cell migration from BM to inflamed tissues	Chemokines CCL-2, CCL-3, CCL-4, CXCL1, IL-8, MIF; adhesion molecules ICAM-1, etc.	TA-MSCs recruit monocytes, macrophages and neutrophils to the tumor microenvironment	Chemokines and cytokines CCL-2, CCL-7, CCL-12, CXCL1, CXCL2, CSF1 etc.
	Myeloid cell and other innate immune cell suppression	MSCs suppress myeloid cell functions upon stimulation by TNFα, IL-1 and ROS	COX-2, PGE2, TSG-6, SOD3, etc.	TA-MSCs polarize the M1 macrophages to an M2 phenotype; TA-MSCs also stimulate MDSC differentiation	CXCL3, HGF etc.
	Myeloid cell reprogramming	MSCs convert M1 macrophages to an M2-like type	PGE2, TSG-6, etc.
	T cell recruitment	MSCs augment T-cell infiltration and activities in a low-level inflammatory environment	Chemokines CXCL9, 10, 11; adhesion molecules ICAM-1, VCAM-1	Not known
	T cell suppression	MSCs exert a robust suppression of T-cells upon stimulation by IFNγ together with other inflammatory cytokines	NO, IDO, PGE2, PD-L1, HO-1, LIF, IL-6, galectin 1, FasL, TGFβ, Treg, etc.	MSCs suppress anti-tumor immunity	NO, IDO, Treg, regulatory CD8+ T cells, etc.
		Wound healing response to injury		Wound healing response to Cancer
		Functions	Mechanisms	Functions	Mechanisms
Proliferation	MSC homing	MSCs efficiently home to tissue injurysites	Chemokines CXCL12, CCL-2, CCL27 and CCL21; VCAM-1; MMPs; etc.	Exogenously implanted and endogenous MSCs efficiently migrate into the tumor environment	CXCL12, CCL-2, CCL-25, CXCL16, MIF, IL-6, LL-37 etc.
	MSC differentiation and fibroplasia	MSCs can be differentiated into osteoblasts, adipocytes and myofibroblasts at the injury sites	TGFβ, BMPs, Notch, Wnt, Hedgehogs, etc.	BM-MSCs or adjacent tissue-derived MSCs give rise to distinct types of tumor-associated myofibroblasts	TGFβ etc.
	Re-epithelialization	MSCs promote epithelial cell growth	Growth factors EGF, HGF, KGF, PDGF, IGF etc.	TA-MSCs support survival of cancer stem cells and proliferation of tumor cells	IL-6, IL-8, CXCL1, CXCL7, BMPs, miRNAs
	Angiogenesis	MSCs enhance angiogenesis	Pro-angiogenic factors VEGF, FGF, PDGF, TGFβ, etc.	TA-MSCs facilitate tumor-associated angiogenesis	VEGF, IL-6, etc.
Tissue remodeling	Inhibition of proliferation	MSCs inhibit tissue cell proliferation	TGFβ, cell-cell contact, MMPs	TA-MSCs suppress epithelial tumor growth but drive them to enter dormancy	TRAIL, DKK-3, cell-cell contact, cannibalization, miR-23b, 127, 197, 222, 223
	Inhibition of angiogenesis	MSCs suppress angiogenesis during tissue remodeling	TIMPs, MMPs	TA-MSCs can inhibit angiogenesis	ROS, inhibition of PDGF signaling
	Collagen rearrangement	MSCs promote ECM remodeling	MMPs, TIMPs, TGFβ	TA-MSCs modulate collagen organization	DDR2, MMPs
	Tissue cell invasion	MSCs stimulate tissue cell invasion	MMPs, collagen rearrangement	TA-MSCs accelerate tumor cell invasion and metastasis	Chemokines CCL-2, CCL-5, CCL-9, CXCL10 etc.; TA-MSCs-induced EMT

Abbreviations: TFs, Tissue factors; FVIII, Factor VIII; MIF, Macrophage migration inhibitory factor; ICAM-1, Intercellular adhesion molecule 1; CCL, CC motif chemokine ligand; CXCL, C-X-C motif chemokine ligand; IL, Interleukin; CSF1, Colony stimulating factor 1; COX-2, Cyclooxygenase-2; PGE2, Prostaglandin E2; TSG-6, Tumor necrosis factor (TNF)-stimulated gene-6; SOD3, Superoxide dismutase 3; HGF, Hepatocyte growth factor; VCAM-1, Vascular cell adhesion molecule 1; NO, Nitric oxide; IDO, Indoleamine 2,3-dioxygenase; PD-L1, Programmed death-ligand 1; HO-1, Heme oxygenase 1; LIF, Leukemia inhibitory factor; FasL, Fas ligand; Treg, Regulatory T cell; EGF, Epidermal growth factor; KGF, Keratinocyte growth factor; PDGF, Platelet-derived growth factor; IGF, Insulin-like growth factor; BMP, Bone morphogenetic protein; miRNA, microRNA; VEGF, Vascular endothelial growth factor; FGF, Fibroblast growth factors; PDGF, Platelet-derived growth factor; TGFβ, Transforming growth factor beta; MMP, Matrix metalloproteinase; TRAIL, TNF-related apoptosis-inducing ligand; DKK-3, Dickkopf WNT Signaling Pathway Inhibitor 3; TIMP, Tissue inhibitor of metalloproteinase; ROS, Reactive oxygen species; DDR2, Discoidin domain receptor 2; EMT, Epithelial–mesenchymal transition.