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.