Table 6 Representative priming MSCs in preclinical and clinical studies

IFN-γ

Bone marrow

graft-versus-host disease (GVHD)

In vivo

IFN-γ primed MSCs significantly reduced the symptoms of GVHD in NOD-SCID mice, thereby increasing survival rate when compared with naïve MSC-infused mice

[146]

IFN-γ

Bone marrow

–

In vitro

Inhibited T cell effector function through the ligands for PD1 and Th1 cytokines production

[148]

IFN-γ

Bone marrow

IDO1, which depletes tryptophan necessary to support proliferation of activated T cells

In vitro

MSCs priming causes chromatin remodeling at the IDO1 promoter, that this alteration is maintained during processing commonly used to prepare MSCs for clinical use and that, once primed, MSCs are poised for IDO1 expression even in the absence of cytokines

[149]

IFN-γ

Bone marrow

–

In vitro

Xenotransplantation of IFN-γ-pretreated human MSCs induces mouse calvarial bone regeneration

[150]

IFN-γ

Bone marrow

DSS-induced colitis model

In vitro/ in vivo (mice)

Attenuated development of colitis, reduced pro-inflammatory cytokine levels in colon and increased migration potential

[151]

IFN-γ

Umbilical cord

–

In vitro

Increased suppression of NK cells and reduced NK-mediated cytotoxicity

[152]

IL-1β

Umbilical cord

DSS-induced colitis model

In vitro/ in vivo (mice)

Attenuated the development of murine colitis, increased migration potential to inflammatory sites by CXCR4 upregulation

[153]

TNF-α and LPS

Bone marrow

–

In vitro

Increased alkaline phosphate activity and bone mineralization

[154]

IL-17A

Bone marrow

–

In vitro

Increased suppressive potential of T cell proliferation correlated with increased IL-6, inhibited surface CD25 and Th1 cytokines expression, and induced iTregs

[155]

5% O2

Wharton’s jelly

–

In vitro

Conditioned-medium increased migration and tube formation in vitro, partially reduced by prior inhibition autophagy

[156]

2.5% O2

Bone marrow

Radiation-induced lung injury model

In vitro/ in vivo (mice)

Upregulated HIF-1α, increased survival and the antioxidant ability, increased efficiency in the treatment of radiation-induced lung injury

[157]

2–2.5% O2

Placenta

–

In vitro

Upregulated glucose transporters, adhesion molecules and increased angiogenic potential

[156]

2% O2

Adipose tissue

Murine hindlimb ischemia model

In vitro/ in vivo (mice)

Enhanced proliferation, survival, and angiogenic cytokine secretion in vivo

[158]

1.5% O2

Bone marrow

Bleomycin-induced pulmonary fibrosis model

In vitro/ in vivo (mice)

Improved pulmonary functions and reduced inflammatory and fibrotic mediators in vivo

[159]

1% O2

Human cord blood

–

In vitro

Increased the survival and pro-angiogenic capacity in ischemia-like environment, induced anti-apoptotic mechanisms, and increased VEGF secretion

[160]

1% O2

Bone marrow

Intramuscular injection into immune-deficient mice

In vitro/ in vivo (mice)

Reduced cell death under serum-deprivation conditions, decreased cytochrome c and HO-1 levels, enhanced survival in vivo

[161]

3D cell culture in collagen-hydrogel scaffold

Umbilical Cord

–

In vitro

Induced chondrogenesis differentiation by increasing expressions of collagen II, aggrecan, COMPS

[162]

3D cell culture in chitosan scaffold

Bone marrow (rat)

–

In vitro

Induced chondrogenesis differentiation by increased production of collagen type II

[163]

3D cell culture of composite combining an affinity peptide sequence (E7) and hydrogel

Bone marrow (rat)

–

In vitro

Increased cell survival, matrix production, and improved chondrogenic differentiation ability

[164]

3D cell culture in hydrogel

bone marrow (Human)

Rat myocardial infarction model

In vitro/ in vivo

The epicardial placement of MSC-loaded POx hydrogels promoted the recovery of cardiac function and structure with reduced interstitial fibrosis and improved neovascular formation

[165]

Encapsulation in hydrogel

Bone marrow (rat)

Diabetic ulcers model

In vitro/ in vivo (rats)

Promoted granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization

[166]

High glucose concentration in the culture medium

Bone marrow

In vitro

Decreased chondrogenic capacity

[167]

Medium from cardiomyocytes exposed to oxidative stress and high glucose

Bone marrow (diabetic mouse)

Diabetes induced with streptozotocin model

In vitro/ in vivo (mice)

Enhanced survival, proliferation and angiogenic ability, increased the ability to improve function in a diabetic heart

[168]

Spheroid formation (different techniques)

Bone marrow

In vitro

Enhanced homogenous cellular aggregates formation and improved osteogenic differentiation (low attachment plates)

[169]

Spheroids formation (hanging-drop)

Bone marrow

Zymosan-induced peritonitis model

In vitro/ in vivo (mice)

Expressed high levels of anti-inflammatory (TSG-6 and STC-1) and anti-tumorigenic molecules compared to 2D culture, suppressed inflammation in vivo

[170]

matrilin-3-primed spheroid generation

Adipose tissue

intervertebral disc (IVD) degeneration

In vitro/ in vivo (rabbit)

Priming MSCs with matrilin-3 and spheroid formation could be an effective strategy to overcome the challenges associated with the use of MSCs for the treatment of IVD degeneration

[171]

Spheroids formation (hanging drop)

Cord blood

Hindlimb ischemia model

In vitro/ in vivo (mice)

Improved engraftment; increased the number of microvessels and smooth muscle α-actin-positive vessels

[172]