Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Table 1 Effects of mesenchymal stem cells on preclinical disease models

Disease	Species	Route of administration	Effect	MSC mechanism of action	Ref.
Skin-graft rejection	Monkey	Systemic	Prolonged skin graft survival	Inhibition of T cell proliferation	[68]
Skin-graft rejection	Mouse	Systemic	Increased rejection	Induction of memory T cell response	[85]
Skin-graft rejection	Mouse	Systemic	Increased rejection	Potential increased T cell alloreactivity	[48]
Graft-v-Host disease	Mouse	Systemic	Disease prevention	Cytokine-induced iNOS to inhibit T cell proliferation	[58]
Graft-v-Host disease	Mouse	Systemic	No clinical benefit	Lack of suppression of donor T cell proliferation	[86]
Skin wound	Mouse	Systemic	Wound healing	M2 polarization , decreased inflammation, increased IL-10	[31]
Acute lung injury	Mouse	Systemic	Protected lungs from injury	Blockade of TNFα and IL-1 production	[87]
Acute lung injury	Mouse	Local	Decreased severity	Down-regulation of inflammation, increased IL-10	[88]
Melanoma	Mouse	Local	Increased tumor growth	Inhibition of tumor-specific T cell response	[89]
MOG35-55 EAE	Mouse	Systemic	Disease amelioration	Inhibition of CD4+ T cell proliferation	[57]
MOG35-55 EAE (severe)	Mouse	Local	Disease worsening	Focal cell mass formation and increased inflammation	[78]
MOG37-50 EAE	Mouse	Systemic	Disease worsening	Increased pro-inflammatory CD8+ T cell frequency in CNS	[77]
Experimental autoimmune neuritis	Mouse	Systemic	No clinical benefit	Unknown	[90]
Rheumatoid arthritis	Mouse	Systemic	Prevention	Reduced T cell proliferation, decreased inflammation, Treg induction	[70]
Rheumatoid arthritis	Mouse	Systemic	No clinical benefit	Accentuation of TH1 response	[91]
Systemic lupus erythematosus	Mouse	Systemic	Multi-organ dysfunction reversal	Suppression of TH17 and induction of Treg	[92]
Type-I-diabetes	Mouse	Systemic	Delayed onset	Promotion of TH2 response	[93]
Inflammatory bowel disease	Mouse	Systemic	Prevention	Decreased neutrophil infiltration	[94]

MSC: Mesenchymal stem cell; MOG: Myelin oligodendrocyte glycoprotein; EAE: Experimental autoimmune encephalomyelitis; TNF-α: Tumor necrosis factor-α.