Table 6.

Representative priming MSCs in preclinical and clinical studies

Stimuli	Source MSCs	Model/disease	In vivo/in vitro	Results	References
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]