Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells: Potential implications for their clinical use

Table 1 Representative priming strategies of mesenchymal stromal/stem cells and their application in preclinical studies

MSCs	Dose	Priming treatments	Study model	Observed therapeutic effects	Ref.
AMSCs	1 × 105 MSCs/5 × 105 PBMCs	IFN-γ	In vitro model of T cell activation and monocyte M1/M2 polarization	Regulation of T cell activation/anergy and induction of M2-like polarized phenotype in monocytes	[40]
BM-MSCs	0.5 × 106 MSCs/mouse	IFN-γ	In vivo model of chronic colitis	Attenuation of inflammation and colitis	[96]
BM-MSCs	NA	IFN-γ; TNF-α	In vitro model of MLR	Inhibition of allogeneic MLR	[97]
CB-MSC-derived EVs	NA	IFN-γ	In vivo model of acute kidney injury and in vitro model of T cell activation	Regulation of T cell activation and amelioration of kidney injury with unprimed MSCs only	[100]
BM-MSCs and CB-MSCs	1 × 106 MSCs/mouse	IFN-γ	In vivo model of GVHD	Reduction of the symptoms of GVHD	[101]
BM-MSCs	1 × 104 MSCs/2 × 103 macrophages	IFN-γ; LPS; TNF-α	In vitro model of monocyte M1/M2 polarization	Induction of monocyte polarization toward an anti-inflammatory M2 phenotype	[102]
UC-MSCs	1 × 106 MSCs/mouse	IFN-γ; TNF-α	In vivo model of GVHD	Reduction of the symptoms of GVHD	[103]
BM-MSCs	2.5 × 105 MSCs/5 × 105 macrophages	IFN-γ; IL-1β	In vitro model of monocyte M1/M2 polarization	Induction of monocyte polarization toward an anti-inflammatory M2 phenotype	[105]
BM-MSC-derived CM	NA	IFN-γ; IL-1α/β; TNF-α	In vitro model of LPS-injured microglial cells	Reduction in the secretion of inflammatory factors	[106]
AdMSCs; BM-MSCs; CB-MSCs.	NA	IFN-γ	In vitro model of T cell activation	Suppression of T cell proliferation	[110]
BM-MSCs	NA	IFN-γ; spheroids	In vitro model of T cell activation	Suppression of T cell activation and proliferation	[112]
BM-MSCs	2 × 106 MSCs/mouse	IFN-γ	Autoimmune encephalomyelitis	Attenuation of pathologic manifestations	[134]
BM-MSCs	1 × 106 MSCs/mL	IFN-γ	In vitro model of T cell activation and in vivo model of colonic wounds	Regulation of T cell activation and acceleration of healing of colonic mucosal wounds	[135]
UC-MSCs	2 × 106 MSCs/mouse	IL-1β	In vivo model of chronic colitis	Attenuation of inflammation and colitis	[98]
UC-MSCs	1 × 106 MSCs/mouse	IL-1β	In vivo model of sepsis	Increase in survival rate	[109]
MSC-derived EVs	40 μg/mouse	IL-1β	In vitro model of monocyte M1/M2 polarization and in vivo model of sepsis	Induction of monocyte M2 polarization and amelioration of sepsis	[111]
AdMSC-derived CM	20 μL/rat	TNF-α	In vivo model of wound healing	Acceleration of wound closure and angiogenesis	[99]
BM-MSCs	1.6 × 106 MSCs/mouse	TNF-α	In vivo model of peritonitis	Attenuation of inflammatory responses	[136]
BM-MSCs	5 × 106 MSCs/rat	IL-25	In vivo model of chronic colitis	Attenuation of inflammation and colitis	[95]
BM-MSCs	1 × 106 MSCs/mL	IL-6	In vivo model of liver fibrosis	Reduction of liver injury and fibrosis	[104]
BM-MSCs	3.91 × 104 MSCs/3.91 × 106 T cells	IL-17	In vitro model of T cell activation	Suppression of T cell proliferation/activation and Th1 cytokines	[108]
AdMSCs	5 × 105 MSCs/mouse	Hypoxia	In vivo model of hindlimb ischemia	Improvement of angiogenesis	[114]
BM-MSC-derived CM	100 μL/mouse	Hypoxia	In vivo model of wound healing	Acceleration of skin wound healing	[120]
BM-MSCs	2.5 × 105 MSCs/mouse	Hypoxia	In vivo model of pancreatic islet transplantation	Reversion of impaired glucose tolerance	[121]
BM-MSCs	5 × 105 MSCs/mouse	Hypoxia	In vivo model of hindlimb ischemia	Improvement of angiogenesis	[139]
AdMSCs	5 × 105 MSCs/mouse	Hypoxia	In vivo model of hindlimb ischemia	Improvement of functional recovery and neovascularization	[140]
AdMSC-derived CM	NA	Hypoxia	In vivo model of partial hepatectomy	Enhanced liver regeneration	[142]
AdMSCs	2 × 106 MSCs/rat	Hypoxia	In vivo model of acute kidney injury	Improvement of angiogenesis and inhibition of ROS generation	[145]
AdMSC-derived CM	100 μL/mouse	Hypoxia	In vivo model of acute kidney injury	Improvement of renal function and reduction of inflammation	[146]
BM-MSCs	1 × 106 MSCs/rat	Hypoxia	In vivo model of lung IRI	Attenuation of pathologic lung injury score by inhibiting inflammation and generation of ROS and anti-apoptotic effects	[147]
BM-MSCs	NA	Hypoxia	In vivo model of radiation-induced lung injury	Improvement of antioxidant ability	[148]
BM-MSCs	1 × 106 MSCs/rat	Hypoxia	In vivo model of myocardial infarction	Improvement of angiogenesis and function	[150]
BM-MSCs	1 × 106 MSCs/mouse	Hypoxia	In vivo model of myocardial infarction	Prevention of apoptosis in cardiomyocytes	[151]
BM-MSC-derived EVs	1 μg of EVs/mouse	Hypoxia	In vivo model of myocardial infarction	Reduction of cardiac fibrosis	[152]
BM-MSC-derived EVs	50 μg of EVs/rat	Hypoxia	In vivo model of cardiac IRI	Reduction of IRI and improvement of cardiomyocyte survival	[153]
BM-MSC-derived EVs	200 μg of EVs/20 g	Hypoxia	In vivo model of myocardial infarction	Improved cardiac repair by amelioration of cardiomyocyte apoptosis	[154]
BM-MSCs	1 × 106 MSCs/rat	Hypoxia	In vivo model of cerebral ischemia	Enhanced angiogenesis and neurogenesis	[157]
BM-MSC-derived CM	100 μg of CM/kg	Hypoxia	In vivo model of traumatic brain injury	Improved neurogenesis, motor and cognitive function	[158]
UC-MSCs	1 × 105 MSCs/rat	Hypoxia	In vivo model of spinal cord injury	Increase in axonal preservation and decrease of apoptosis	[159]
PMSC-derived CM	100 μL/mouse	Hypoxia	In vivo model of scar formation	Reduction of scar formation	[162]
BM-MSCs	5 × 106 MSCs/rat	Hypoxia	In vivo model of partial hepatectomy	Enhanced liver regeneration	[164]
DP-MSCs	N.A.	Hypoxia	In vivo model of dental pulp injury	Regeneration of dental pulp with a rich vasculature	[167]
AF-MSC-derived CM	N.A.	Hypoxia	In vivo model of wound healing	Acceleration of skin wound healing	[168]
AMSC-derived CM and EVs	200 μL CM and 5 μg EVs/1 × 105 PBMCs, and 100 μL CM and 5 μg EVs/1 × 104 HUVECs	3D cultures/spheroids	In vitro model of T cell activation and HUVEC cells	Induction of angiogenesis and inhibition of T cell proliferation	[44]
AMSCs	250 μL CM/ 1.5 × 105 alveolar epithelial cells	3D cultures/spheroids	In vitro model of lung IRI	Attenuation of IRI side effects by improving the efficacy of in vitro EVLP	[59]
AMSC-derived CM	50 μL CM/ 1 × 104 liver cells	3D cultures/spheroids	In vitro model of liver IRI	Attenuation of IRI side effects by inhibiting inflammation and apoptosis	[131]
BM-MSCs	3 × 106 MSCs/mouse	3D cultures/spheroids	In vivo model of peritonitis	Production of anti-inflammatory cytokines	[137]
BM-MSCs	1.5 × 106 MSCs/mouse	3D cultures/spheroids	In vivo model of peritonitis	Attenuation of inflammatory responses	[138]
CB-MSCs	1 × 107 MSCs/mouse	3D cultures/spheroids	In vivo model of hindlimb ischemia	Improvement of survival and angiogenesis	[141]
AdMSCs	2 × 106 MSCs/rat	3D cultures/spheroids	In vivo model of acute kidney injury	Reduction of apoptosis and tissue damage, promotion of vascularization, and amelioration of renal function	[143]
UC-MSC-derived EVs	200 μg of EVs/mouse	3D cultures/spheroids	In vivo model of acute kidney injury	Attenuationof pathological changes and improvement of renal function	[144]
BM-MSCs	2 × 106 MSCs/rat	3D cultures/spheroids	In vivo model of myocardial infarction	Promotion of cardiac repair	[155]
BM-MSCs	5 × 105 MSCs/rat	3D cultures/spheroids	In vivo model of myocardial infarction	Stimulation of a vascular density and improvement of cardiac function	[156]
AdMSCs	1 × 107 MSCs/mouse	3D cultures/spheroids	In vivo model of hindlimb ischemia	Improvement of angiogenesis	[163]
AdMSCs	2 × 106 MSCs/rabbit	3D cultures/spheroids	In vivo model of disc degeneration	Induction of disc repair	[169]
BM-MSCs	NA	3D cultures/spheroid	In vivo model of bilateral calvarial defects	Induction of bone regeneration	[170]
SMSCs	NA	3D cultures/spheroid	In vivo model of osteochondral defects	Induction of cartilage regeneration	[171]

MSCs: Mesenchymal stem cells; BM-MSCs: Bone marrow-derived mesenchymal stem cells; AMSCs: Amnion-derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; AdMSCs: Adipose-derived mesenchymal stem cells; CB-MSCs: Cord blood-derived mesenchymal stem cells; WJ-MSCs: Wharton’s Jelly-derived mesenchymal stem cells; PMSCs: Placenta-derived mesenchymal stem cells; AF-MSCs: Amniotic fluid derived mesenchymal stem cells; SMSCs: Synovial derived mesenchymal stem cells; EVs: Extracellular vesicles; CM: Conditioned medium; NA: Not available; GVHD: Graft-versus-host disease; IRI: Ischemia-reperfusion injury; 3D: Three-dimensional; IFN: Interferon; TNF: Tumor necrosis factor; IL: Interleukin; MLR: Mixed lymphocyte reactions; LPS: Lipopolysaccharide; HUVEC: Human umbilical vein endothelial cell.