Table 2 Preclinical studies related to preconditioning of MSCs

Human BM-MSCs

Hypoxia

GvHD (mice)

Increase in stemness factors:

Kruppel like factor 4 (KLF4),

Octamer-binding transcription factor 4 (OCT4),

v-myc avian myelocytomatosis viral oncogene

Homolog (C-MYC),

Increase in chemokine genes- CCL2, and CXCL10

Enhanced chemotaxis, viability and homing

[90]

Murine BM-MSCs

Hypoxia

Cellular cardiomyoplasty

Increase in anti-inflammatory cytokine expression as compared to pro-inflammatory cytokines

Improved cardiac function

[91]

Human BM-MSCs

Hypoxia

Limb ischemia (murine)

Reduced NK cell cytotoxicity

Enhanced angiogenesis

[92]

Rat BM-MSCs

Hypoxia

Diabetic cardiomyopathy (Rat)

Upregulation of Bcl-2/Bax ratio,

Inhibited expression and

Activation of caspase 3

Anti-apoptotic

Improved cardiac function

[93]

Human BM-MSCs

IFN-γ

Induced colitis (mice)

Increase in levels of IDO, iNOS

Decrease in T cell proliferation,

Decrease in inflammatory markers:

TNF-a, IL-6, IL-17A

Decrease in disease score and diminished the severity of colitis

[94]

Murine BM-MSCs

IFN- γ

GvHD (murine)

GvHD mortality

Decrease in GvHD score after IFN- γ treatment at high concentrations

[95]

Human Wharton jelly MSCs

IFN- γ

Autoimmune encephalomyelitis (mice)

Increase in immunosuppressive factors: TGF-β, VEGF, HGF and IL-10, IL-4,

Increase in T regulatory cells,

Decrease in inflammatory factors- IL 17A

Decrease in disease score

[96]

Human BM-MSCs

IFN- γ

GvHD (Humanized mice)

T cell apoptosis and anergy

Reduced GvHD pathology and prolonged survival

[97]

UC-MSCs

TLR3 (poly I:C)

Trinitrobenzene sulfonate (TNBS)-induced colitis model (murine)

Reduced production of Th1/17 signature cytokines:

IFN-γ, IL-17A, IL-21, and IL-23,

Increased IL-10 production in the colon,

Increased localization of Treg in colon

Decreased infiltration of pathogenic Th1/17 subsets;

Enhanced migration of UC-MSCs to inflammatory

Sites,

PGE2 mediated inhibition of mononuclear cell

Proliferation

Enhanced immunosuppressive protective effect of UC-MSCs on experimental colitis

[98]

UC-MSCs

TLR3 (poly I:C) and TLR4 (LPS) priming

Dextran sulfate sodium-induced colitis model (murine)

TLR3 priming: inhibited T cell proliferation, Higher expression of IDO,

TLR4 priming: Higher expression of proinflammatory cytokines- IL-6 and IL-8

Poly(I:C) primed

UC-MSCs significantly ameliorated clinical and histopathological severity of DSS-induced colitis

[99]

Murine BM-MSCs

TLR1/2 (Pam3CSK4),

TLR2 (PGN),

TLR3 (polyI:C),

TLR4 (LPS),

TLR5 (flagellin),

TLR2/6 (FSL-1),

TLR7/8 (R848),

TLR9-ODN 1826

Dextran sulfate sodium-induced colitis model (murine)

TLR3 priming: increased IDO expression

Poly(I:C)-treated MSCs attenuated the pathologic severity of DSS-induced murine colitis

[100]

Murine BM- MSCs

TLR3 (poly I:C) and TLR4 (LPS) priming

Experimental autoimmune encephalomyelitis (murine)

TLR 3 priming: reduced proliferation of CD3+ T cells, reduced \differentiation/activation of proinflammatory lymphocytes, Th1 and Th17

TLR4 priming: Increased CD3+ T-cell proliferation, induced Th1 and Th17 cells,

Increased levels of proinflammatory cytokine IL-6

Pre-treatment of MSCs with poly(I:C) improved their therapeutic immunosuppressive abilities

[101]