Table 1.
Representative MSC-derived EVs with anti-inflammatory properties
| Indication | EV source and Isolation method | Therapeutic schedule | Effective molecules | Treatment outcome |
|---|---|---|---|---|
| Respiratory | ||||
| Influenza 95 | Swine BM-MSC; Differential centrifugation with ultracentrifugation |
80 μg/kg body weight, single dose; intratracheal | RNAs | -Reduced virus shedding and influenza virus replication -Reduced apoptosis and proinflammatory cytokines -Ameliorated influenza virus-induced acute lung injury |
| Neonatal hyperoxic lung injury 96 | Human UC-MSC; Differential centrifugation with ultracentrifugation |
20 μg, single dose; intratracheal | VEGF protein and mRNA | -Suppressed macrophage activation and proinflammatory cytokines secretion -Improved alveolarization and angiogenesis -Attenuated hyperoxic lung injuries |
| Pneumonia 97 |
Human BM-MSC; Differential centrifugation with ultracentrifugation |
dosed by total cell count, single dose; intratracheal or intravenous | KGF mRNA | -Reduced inflammatory cell infiltration and cytokines secretion -Increased bacterial clearance -Prolonged survival |
| Allergic airway inflammation 98 | Human iPSC-MSCs; Anion-exchange chromatography |
2×1010 particles, single dose; intravenous | miR-146a-5p | -Inhibited the function of human ILC2s in vitro -Alleviated ILC2 levels, inflammatory cell infiltration and mucus production in the lung, and improved airway hyperresponsiveness |
| Cardiovascular | ||||
| Myocardial I/R injury 99 | Mouse BM-MSC; Differential centrifugation with ultracentrifugation |
20 μg, single dose; myocardial injection | miR-182 | -Converted pro-inflammatory macrophages to M2-like phenotype -Reduced infarct size and alleviated inflammation |
| Myocardial infarction 100 | BM-MSC; ExoQuick-TC (System Bioscience) |
80 μg, single dose; myocardial injection | Not studied | -Promoted angiogenesis and inhibited proliferation of lymphocytes in vitro -Reduced infarct size, and preserved cardiac systolic and diastolic performance |
| Sepsis-induced cardiac injury 101 | Mouse BM-MSC; Differential centrifugation with ultracentrifugation |
2 μg/g body weight, single dose; intravenous | miR-223 | -Reduced polymicrobial sepsis triggered cardiac dysfunction, apoptosis and inflammatory response |
| Hepatic | ||||
| Hepatic I/R injury 102 | Human UC-MSC; Differential centrifugation with ultracentrifugation |
10 mg/kg body weight, single dose; intravenous | MnSOD | -Alleviated neutrophil infiltration and oxidative stress -Protected against hepatic apoptosis and restored liver function |
| Chronic liver failure 103 |
Human ESC-MSCs; Differential centrifugation with ultracentrifugation |
350 μg, single dose; intraperitoneal | Not studied | -Hydrogel-mediated delivery improved the anti-fibrosis, anti-inflammation, anti-apoptosis, and regenerative effects of MSC-EVs |
| Acute liver failure 104 |
Human and mouse BM-MSC; Differential centrifugation with ultracentrifugation |
2×108~2×1010 particles, single dose; intravenous/ intraperitoneal | Y-RNA-1 | -Reduced hepatic injury, modulated cytokine expression, and increased survival by systemic administration |
| Renal | ||||
| Renal I/R injury 105 | Mouse BM-MSC; Differential centrifugation with ultracentrifugation |
80 μg, single dose; renal capsule injection | Not studied | -Hydrogel-mediated delivery enhanced the anti-apoptosis and anti-inflammatory effects of MSC-EVs -Promoted endothelial cell proliferation and angiogenesis, and inhibited chronic renal fibrosis |
| Metabolic syndrome and renal artery stenosis 106 | Swine AD-MSC; Differential centrifugation with ultracentrifugation |
1×1010 particles, single dose; intrarenal injection | IL-10 | -Induced monocytes to differentiate into M2-like macrophages, and reduced renal inflammation -Ameliorated renal hypoxia and scarring |
| Renal I/R injury 107 | Human UC-MSC; Differential centrifugation with ultracentrifugation |
100 μg, single dose; intravenous | miR-15a miR-15b miR-16 |
-Suppressed CX3CL1 expression, macrophage infiltration and cell apoptosis -Improved renal function and renal fibrosis |
| Renal I/R injury 108 | Human UC-MSC; Differential centrifugation with ultracentrifugation |
100 μg, single dose; intravenous | miRNAs | -Improved tubular injury and protected renal functions by modulating NK cells |
| Neurological | ||||
| Cortical injury 109 | Monkey BM-MSC; Differential centrifugation with ultracentrifugation |
4×1011 particles, two doses (Day 1 and 14 post-injury); intravenous | Not studied | -Reduced neuroinflammation and shifted microglia towards an anti-inflammatory phenotype -Recovered motor function |
| Hippocampal damage 110 | Human BM-MSC; Differential centrifugation with ultracentrifugation |
15 μg, two doses; intracardiac injection | Cytokines and factors | -Suppressed extensive inflammation, reactive astrogliosis, and increased integrity of the BBB -Rescued memory and learning deficiencies |
| Multiple sclerosis 111 | Human BM-MSC; Differential centrifugation with ultracentrifugation |
150 μg, single dose; intravenous | RNAs and proteins | -Decreased neuroinflammation and upregulated Tregs -Reduced demyelination and the clinical score of EAE mice |
| Acute spinal cord injury 112 | Human BM-MSC; Tangential flow filtration |
1×109 particles, single dose; intravenous | Not studied | -Diminished inflammatory response with apparent astrocyte and microglia disorganization, and improved functional recovery |
| Preterm brain injury 113 |
Human BM-MSC; Differential centrifugation with ultracentrifugation |
dosed by total cell count, two doses (3 h before and 24 h after injury); intraperitoneal | Not studied | -Prevented reactive astrogliosis and microgliosis -Reduced neuronal cell death, and restored white matter microstructure |
| Musculoskeletal | ||||
| Osteoarthritis 114 |
Human ESC-MSCs; Tangential flow filtration |
100 μg, three doses (2, 4, and 8-weeks post-injury); intra-articular injection | Not studied | -Suppressed inflammation, apoptosis and matrix degradation -Promoted TMJ repair and regeneration |
| Inflammatory arthritis 115 | Mouse BM-MSC; Differential centrifugation with ultracentrifugation |
250 ng of Exos, 250 or 600 ng of MPs, two doses (Day 18 and post-injury); intravenous | Not studied | -Exerted an anti-inflammatory role on T and B lymphocytes -Exos were more efficient in suppressing inflammation in vivo |
| Articular cartilage 116 | Human ESC-MSCs; Tangential flow filtration |
100 μg, once a week for up to 12 weeks; intra-articular injection | CD73 | -Induced the polarization of M2-like macrophages, and reduced pro-inflammatory cytokine production -Enhanced cellular proliferation and chondrocyte functions |
| Duchenne muscular dystrophy 117 | Placenta-MSC; Differential centrifugation with ultracentrifugation |
5×109 particles, single dose; intra-muscular injection | miR-29c | -Promoted muscle differentiation in vitro -Decreasing inflammation and fibrosis in mdx mice |
| Skeletal muscle damage 118 | Human AD-MSC; Differential centrifugation with ultracentrifugation |
total 2×1010 particles: 1×1010 (immediately after injury), intravenous; 0.5×1010 (Day 1 and 2 post-injury), intra-muscular injection | neuregulin 1 protein | -Impaired inflammatory cell infiltration -Induce vascular growth and protect muscle against I/R damage |
| Skeletal muscle damage 119 | Human AD-MSC; Differential centrifugation with ultracentrifugation |
1 μg, single dose; intra-muscular injection | miRNAs | -Triggered macrophage polarization from a M1 to a M2 phenotype -Downregulated the pro-inflammatory cytokine IL-6 accompanied by the upregulation of IL-10 |
| Others | ||||
| Obesity 120 | Mouse AD-MSC; ExoQuick-TC (System Bioscience) |
30 μg, once every 3 days for 6-8 weeks; intraperitoneal | STAT3 protein | -Polarized macrophages toward M2 expressing high levels of arginase-1 and IL-10 -Alleviated white adipose tissue inflammation, obesity, and hepatic steatosis, and improved metabolic homeostasis |
| Inflammatory bowel disease 121 | Human BM-MSC; Differential centrifugation with ultracentrifugation |
200 μg, single dose; intravenous | metallothionein-2 protein | -Downregulated inflammatory responses and maintained intestinal barrier integrity -Polarized M2b macrophages and subsequently induced IL-10 secretion |
| Retinal I/R injury 122 | Human BM-MSC; Ultrafiltration followed by ExoQuick-TC (System Bioscience) |
4×106 particles, single dose; vitreous humor injection | Not studied | -Enhanced functional recovery, and decreased neuro-inflammation and apoptosis |
| Esophageal fistula 123 | Swine AD-MSC; Differential centrifugation with ultracentrifugation |
PF-127 gel containing 5.2×1011 particles injected through fistula internal and external orifices, respectively | Not studied | -Reduced the density of myofibroblasts -Decreased fibrosis and inflammatory response -Increased angiogenesis. |
| Burn 124 | Human UC-MSC; PureExo® Exosome Isolation Kit (101Bio) |
800 μg (RNA concentration), single dose; intravenous | miR-181c | -Reduced burn-induced inflammation by downregulating the TLR4 signaling pathway |
AD, adipose tissue; BM, bone marrow; UC, umbilical cord; iPSC, induced pluripotent stem cell; ESC, embryonic stem cell; ILC2, Group 2 innate lymphoid cell; I/R, ischemia/reperfusion; EAE, experimental autoimmune encephalomyelitis; TMJ, temporomandibular joint; Exo, exosome; MP, microparticle; VEGF, vascular endothelial growth factor; KGF, keratinocyte growth factor; MnSOD, manganese Superoxide dismutase.