Table 1.
Therapeutic potential of MSC exosomes in the context of regenerative medicine
| Condition | MSC source | Isolation method | Mechanism | Main outcome | Ref |
|---|---|---|---|---|---|
| MI | Cardiac MSC | Precipitation at 4C with 5 polyethylene glycol 4000 | Transferring miRs | Promoting cardiac angiogenesis and activating cardiomyocyte proliferation (animal study) | [88] |
| MI | BM-MSC | ExoQuick Exosome Precipitation Solution | Delivering miR-221 and miR-19a | Higher protective effects in cardiomyocytes promoted the growth of cardiomyocytes and prevented cell apoptosis (animal study) | [89, 90] |
| MI | BM-MSC | Ultracentrifugation (110,000g) | Delivering miR-210 that decreases the expression of ephrin-A3 | Promoted angiogenesis and cardiac function (animal study) | [91] |
| Myocardial IRI | HuES9.E1-derived MSC | Chromatography columns | Stimulating anti-apoptotic pathways and also inhibiting pro-apoptotic pathways | Enhanced bioenergetics and pro-survival signaling of cardiac cells (animal study) | [92] |
| MI | BM-MSC | ExoQuick-TC | n.a | Inducing neovascularization and suppressing inflammatory response (animal study) | [93] |
| MI | BM-MSC | Ultracentrifugation (200,000g) | Delivering MiR-125b-5p | Inhibited apoptosis of cardiomyocyte through inhibition of pro-apoptotic genes p53 and BCL2-antagonist/killer 1 (BAK1) (animal study) | [94] |
| Autoimmune hepatitis | BM-MSC | Ultracentrifugation (100,000g) | Delivering exosomal miR-223 | Downregulating various inflammatory genes and proteins and inhibition of hepatocyte death (animal study) | [95] |
| Hepatic oxidant injury | UC-MSC | Ultracentrifugation (100,000g) | Delivering glutathione peroxidase 1 (GPX1) | Suppressed oxidative stress and apoptosis on CCl4-and H2O2-induced hepatic damage (animal study) | [96] |
| LF | HuES9.E1-derived MSC | High-performance liquid chromatography (HPLC) | Increasing the expression of cyclin D1 and PCNA as proliferative proteins and enhancing expression of Bcl-xL as an anti-apoptotic factor | Promoting hepatocyte proliferation and inhibiting hepatocyte apoptosis (animal study) | [97] |
| Liver fibrosis | BM-MSC | Ultracentrifugation (100,000g) | Lowering the plasma level of alanine aminotransferase and modulating expression level of inflammatory cytokines and regulatory T cells | Inducing hepatoprotective and anti-inflammatory effects (animal study) | [98] |
| LF | ESC-MSC | Ultracentrifugation (100,000g) | n.a | Enhanced anti-apoptosis, anti-fibrosis, and regenerative capacity (animal study) | [99] |
| LF | BM-MSC | Ultracentrifugation (100,000g) | Delivering Y-RNA-1 | Modulated inflammatory response and by inducing multiple anti-apoptotic genes (animal study) | [100] |
| AD | WJ-MSC | Ultracentrifugation (100,000g) | Delivering catalase | Decreasing neuronal oxidative stress and synapse damage (animal study) | [101] |
| Brain stroke | BM-MSC | Ultracentrifugation (100,000g) | Transferring miR-133b to neighboring astrocytes and neuron cells | Increased functional regeneration (animal study) | [102] |
| SCI | BM-MSC | n.a | Enhanced neuro-vascularization and weaken neuronal apoptosis, as well as prevent inflammation and inhibit the neurotoxic of A1 astrocytes | Boosted SCI functional recovery (animal study) | [103] |
| SNI | UC-MSCs | Ultracentrifugation | Promoted the generation of axons and Schwann cells, minimized muscular atrophy, and induced anti-inflammatory reactions | Improved functional recovery and peripheral nerve regeneration (animal study) | [104] |
| SNI | Gingiva MSC | ExoQuick Exosome Precipitation Solution (SBI Systems Biosciences) | Expression of phenotype-related genes, c-Jun, Notch1, GFAP, Sox2 and the stimulation of JNK pathways | Regeneration of peripheral nerve (animal study) | [105] |
| MS | AT-MSC | Ultracentrifugation (100,000g) | Reducing the number of Iba-1-positive microglial cells and also the plasma levels of inflammatory cytokines | Modulated microglial activity and improved immunomodulatory activities (animal study) | [88] |
| AKI | UC-MSCs | Ultracentrifugation (100,000g) | Transferring hepatocyte growth factor (HGF) mRNA | Improved dedifferentiation and proliferation of damaged cells (animal study) | [89] |
| Kidney IRI | n.a | n.a | Delivering miR-22 for mTOR/HIF feedback interaction pathway and suppressing (PDCD4)/NFKB pathways | Stimulating kidney protection by inducing anti-inflammatory responses and reducing epithelial cell damage (animal study) | [106] |
| Kidney IRI | WJ-MSC | Ultracentrifugation (100,000g) | Reduced kidney cell apoptosis and boosted anti-inflammatory responses | Downregulated CX3CL1 expression and improved kidney function (animal study) | [107] |
| AKI | UC-MSCs | Ultracentrifugation (100,000g) | Activation of the ERK 1/2 pathway and inhibition of the p38MAPK pathway | Suppressing oxidative stress, inducing cell growth, and reducing kidney cell apoptosis (animal study) | [108] |
| CKD | Urinary MSC | Ultracentrifugation (100,000g) | Delivering effective growth factors | Inhibited cell apoptosis and increased vascular regeneration (animal study) | [109] |
| Kidney artery stenosis | AT-MSC | n.a | Delivering anti-inflammatory cytokine interleukin (IL) 10 | Attenuated kidney inflammation and fibrosis, increased kidney blood supply, and suppressed glomerular filtration (animal study) | [110] |
| Kidney fibrosis | BM-MSC | ExoQuick Exosome Precipitation Solution | Delivering exogenous microRNA let7c | Suppression of kidney inflammation (animal study) | [111] |
| ALI | UCB-MSC | Ultracentrifugation (100,000g) | Delivering VEGF | Restored impaired alveoli function, angiogenic effects, and anti-inflammatory responses and minimized cell apoptosis (animal study) | [112] |
| ALI | AT-MSC | Ultracentrifugation | Delivering miRNA | Attenuating ALI damage and macrophages polarization (animal study) | [113] |
| Lung IRI | BM-MSCs | n.a | Transferring miR-21-5p | Inhibited lung edema and improved the function of wound healing (animal study) | [114] |
| ALI | BM-MSC | Ultracentrifugation | Transferring KGF | Promoted immunomodulatory effects and increased intracellular ATP levels of alveolar epithelial type 2 cell (animal study) | [115] |
| ALI | BM-MSC | Ultracentrifugation (100,000g) | Transferring mitochondrial | Inhibited the production of inflammatory cytokines and enhanced phenotype 2 of alveolar macrophages (animal study) | [116] |
| PAH | BM-MSC | Ultracentrifugation (100,000g) | Alleviated pressure, inhibited right ventricle hypertrophy, and restored pulmonary function | Improved pulmonary artery hypertension (animal study) | [117] |
Note: ALI acute lung injury, MI myocardial infarction, LF liver failure, IRI ischemia-reperfusion injury, PAH pulmonary arterial hypertension, AKI acute kidney injury, CKD chronic kidney disease, SCI spinal cord injury, SNI spared nerve injury, AD Alzheimers diseases, MS multiple sclerosis, BM bone marrow, AT adipose tissue, UC umbilical cord, UCB umbilical cord blood, WJ Whartons jelly, miRs microRNAs, n.a not available