Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications
Abstract
:1. Introduction
2. EV Biogenesis and Characterisation
3. EV Isolation Methods
4. MSC-EVs in Tissue Engineering and Regeneration
4.1. Nervous Regeneration
4.2. Cardiac Regeneration
4.3. Bone Regeneration
4.4. Cartilage Regeneration
4.5. Kidney Regeneration
4.6. Liver Regeneration
4.7. Muscle Regeneration
4.8. Wound Healing
4.9. The Regenerative Effect of MSC-EVs on Various Tissues
5. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Injury/Damage | Cell Source | Isolation Method | Administration Route/Quantity | Main Findings from Studies Evaluating These EVs |
---|---|---|---|---|
Nervous System | ||||
Sciatic peripheral nerve crush | Rat BMMSCs | Ultracentrifugation (100,000× g) | Injection/45 μg total EV protein in 30 μL PBS | Improved sciatic function index, enhanced histomorphometric repair in nerve regeneration and increased GAP-43 expression [50] |
Sciatic peripheral nerve crush | Human UCMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/100 μg total EV protein | Generation of axons and Schwann cells, reduction of denervated muscle atrophy and modulation of inflammation [51] |
Sciatic peripheral nerve crush | Rat ADMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/details not provided | Peripheral nerve regeneration and neurite growth in sciatic nerve defects through Schwann cell (SC) modulation [52] |
Peripheral nerve injury (in vitro) | Rat ADMSCs | Total Exosome isolation reagent kit (Invitrogen) | 2 and 8 µg total EV protein | Enhanced proliferation of Schwann cells in the site of peripheral nerve injuries via internalisation [53] |
Sciatic peripheral nerve crush | Human gingiva MSCs | ExoQuick-TC kit (System Biosciences) | EV-scaffold transplantation/40 μg total EV protein in 20 μL PBS | Enhanced proliferation and migration of Schwann cells via the activation JNK pathway and the up-regulation of c-JUN, Notch1, GFAP and SOX2 [54] |
Cerebral artery stroke (in vitro) | Rat BMMSCs | Sucrose gradient ultracentrifugation (100,000× g) | Details not provided | Neurite outgrowth by transfer of miR-133b to neural cells [55] |
Cerebral artery stroke | Rat BMMSCs | Sucrose gradient ultracentrifugation (100,000× g) | Injection/100 μg total EV protein in 500 μL PBS | Increased axonal density and synaptophysin-positive areas along the ischemic boundary zone of the cortex and striatum [58] |
TBI | Rat BMMSCs | ExoQuick-TC kit (System Biosciences) | Injection/100 μg total EV protein in 500 μL PBS | Improved recovery of brain function by increasing the number of number of neurons and endothelial cells in the lesion boundary zone and dentate gyrus [59] |
SCI | Mouse BMMSCs | Differential centrifugation and sequential ultracentrifugation (up to 110,000× g) | Injection/200 μL derived from 1 × 106 MSCs post-SCI and 200 μL derived from 1 × 106 MSCs at 1-day post-injury | Reduced migration of pericytes and improved structural integrity of the BSCB [62] |
SCI | Rat BMMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/200 μg total EV protein in 200 μL PBS | Reduced neuronal apoptosis through the activation of the Wnt/β-catenin signalling pathway [63] |
SCI | Rat BMMSCs | ExoQuick-TC kit (System Biosciences) | Injection/100 μg total EV protein in 500 μL PBS | Modification of rat BMMSC-EVs with miR-133b activated the ERK1/2, STAT3 pathway, which resulted to enhanced neuron preservation [64] |
MS | Human placental MSCs | Differential centrifugation and ultracentrifugation (112,700× g) | Injection/1 × 107 or 1 × 1010 particles in 200 μL PBS | Increased myelination in the spinal cord of treated mice and improved motor function [65] |
EAE | Human BMMSCs | Differential centrifugation and ultracentrifugation (120,000× g) | Injection/150 μg of total EV protein | Reduced neuroinflammation, demyelination and improved motor function |
Alzheimer’s disease | Details not included | Differential centrifugation and ultracentrifugation (110,000× g) | Injection/10 µg total EV protein in 2 µL PBS | Enhanced neurogenesis and cognitive function recovery [67] |
Cardiac | ||||
MI | Human embryonic MSCs | Sucrose gradient ultracentrifugation (200,000× g) | Injection/3 µg total EV protein in 200 µL PBS | Reduced infarct size [71] |
MI | Human embryonic MSCs | Tangential flow filtration | Infusion/0.4 μg total EV protein in 1 mL PBS | Increased myocardial viability and inhibited adverse remodelling [72] |
MI | Human UCMSCs | Sucrose gradient ultracentrifugation (100,000× g) | Infusion/400 µg of total EV protein | Akt-modified MSC-EVs promoted endothelial cell proliferation, migration, tube-like structure formation, and blood vessel formation [73] |
MI | Murine iPSCs | Differential centrifugation and ultracentrifugation (110,000× g) | Injection/100 µg of total EV protein in 30 μL PBS | Increased cardiac repair, left ventricular function, vascularization, and reduced apoptosis and hypertrophy [74] |
MI | Human amniotic fluid-derived MSCs | Serial ultracentrifugation | Injection/4.5 μg total EV protein | Improved cardiac regeneration via paracrine modulation of endogenous mechanisms [75] |
MI | Rat BMMSCs | Differential centrifugation and ultracentrifugation (120,000× g) | Injection/10 μg total EV protein in 100 μL PBS | BMMSCs and their derived EVs synergistically improved cardiac function, reduced infarct size, and increased neovascularization [76] |
MI | Human BMMSCs | Ultracentrifugation (100,000× g) | Injection/80 μg total EV protein | Hypoxia-elicited BMMSC-EVs showed higher cardiac regeneration as compared to MSC-EVs isolated in normoxia [79] |
MI | Murine BMMSCs | Differential centrifugation and ultracentrifugation (140,000× g) | Injection/200 µg of total EV protein in 200 μL PBS | Hypoxia-elicited BMMSC-EVs prevented cardiomyocyte apoptosis through the enrichment of miR-125b-5p [80] |
MI | Rat BMMSCs | Repeated ultracentrifugation | Injection/EVs derived from 2 × 107 MSCs, in 30 μL PBS | Hypoxia-elicited BMMSC-EVs enhanced the cardioprotective actions of EVs [81] |
MI | Human UCMSCs | Total exosome isolation kit (Life Technologies) | EV-hydrogel transplantation/20 µg of total EV protein in 20 μL PBS | Sustain delivery of MSC-EVs improved myocardial function by reducing inflammation, fibrosis and apoptosis, and by promoting angiogenesis [82] |
Bone | ||||
Critical-sized calvarial defect | Human BMMSCs | Differential centrifugation and ultracentrifugation (120,000× g) | EV-hydrogel transplantation/100 μg of total EV protein in 50 μl PBS | Increased angiogenesis and bone formation [83] |
Critical-sized calvarial defect | Human iPSCs | Ultrafiltration and gradient ultracentrifugation (100,000× g) | EV-scaffold transplantation/100 μg or 200 μg of total EV protein | Increased angiogenesis, osteogenesis and bone formation [84] |
Critical-sized calvarial defect | Human BMMSCs | Differential centrifugation and ultracentrifugation (110,000× g) | Injection to implanted scaffolds/100 μg of total EV protein in 200 μL PBS | BMMSC-EVs modified with dimethyloxaloylglycin enhanced bone regeneration through Akt/mTOR pathway activation and angiogenesis stimulation [85] |
Bone regeneration (in vitro) | Human ADMSCs | Ultracentrifugation (100,000× g) | Details not provided | TNFα-primed ADMSC-EVs enhanced proliferation and differentiation of osteoblastic cells by increasing the expression of Wnt-3a [86] |
Femoral shaft fracture(CD9−/− and wild types) | Human BMMSCs | Ultracentrifugation (180,000× g) | Injection / details not provided | Improved fracture healing in CD9−/− mice, and accelerated bone repair in wild types [87] |
Tooth root slice | Human dental pulp MSCs | ExoQuick-TC kit (System Biosciences) | Injection/details not provided | Increased odontogenic differentiation regeneration of dental pulp-like tissue [88] |
Periodontal defect | Unknown | Tangential flow filtration | EV-scaffold transplantation/40 μg of total EV protein | Enhanced periodontal ligament cell migration, proliferation and periodontal regeneration [89] |
Critical-sized skull defect | Human ADMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | EV-scaffold transplantation/1 μg of total EV protein in 1 μL PBS | MSC-EVs immobilised in poly(lactic-co-glycolic acid) stimulated the controlled release of EVs promoting MSC migration and homing in the bone defects [90] |
Ectopic bone formation | Human ADMSCs | Differential centrifugation | EV-scaffold transplantation/10 μg of total EV protein in 1 mL PBS | MSC-EV immobilised constructs showed higher osteo-inductive ability and long-term stability for bone graft modification [91] |
Critical-sized calvarial defects | Human BMMSCs | Differential centrifugation and sucrose gradient ultracentrifugation (100,000× g) | EV-scaffold transplantation/5 × 1011 or 1 × 1012 particles in 1 mL PBS | BMMSC-EVs loaded into tricalcium phosphate scaffolds promoted osteogenesis activity and bone regeneration [92] |
Ectopic bone formation | Rat BMMSCs | Differential centrifugation | EV-scaffold transplantation/20 μg of total EV protein in 20 μL PBS | MSC-EVs loaded into decalcified bone matrix scaffolds stimulated neo-vascularization and bone formation [93] |
Cortical calvaria bone defect | Human gingival MSCs | ExoQuick-TC kit (System Biosciences) | EV-scaffold transplantation/details not provided | MSC-EVs loaded in three-dimensional polylactic acid scaffolds enhanced osteogenic properties and improved bone healing [94] |
Cartilage | ||||
OA | Human amniotic fluid MSCs | Total exosome isolation kit (Life Technologies) | Injection/100 μg of total EV protein | EV-treated defects showed superior pain tolerance level and improved histological scores than the MSC-treated defects [96] |
Cartilage regeneration (in vitro) | Human BMMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Details not provided | Increased production of collagen type II and proteoglycans in chondrocytes isolated from OA patients [97] |
OA | Human BMMSCs | Differential centrifugation and sucrose gradient ultracentrifugation (100,000× g) | Injection/500 μg of total EV protein in 1 mL PBS | BMMSC-EVs modified with miR-92a-3p, suppressed cartilage degradation by targeting the WNT5A and promoted cartilage repair [100] |
OA | Rat MSCs | Tangential flow filtration | Injection/1 × 1011 particles in 1 mL PBS | TGFβ primed MSC-EVs promoted cartilage tissue repair through Sp1 regulation [101] |
OA | Human embryonic MSCs | Tangential flow filtration | Injection/100 µg of total EV protein in 100 µL PBS | Increased chondrocyte proliferation, reduced apoptosis, regulated inflammation and matrix homeostasis [102,103,104] |
OA | Human embryonic MSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/details not provided | Improved osteoarthritis through balancing the synthesis and degradation of cartilage ECM [105] |
Cartilage defect | Human UCMSCs | Differential centrifugation and ultracentrifugation (110,000× g) | Injection/1 × 1010 particles in 1 mL PBS | UCMSCs cultured in a bioreactor resulted in a higher yield of EVs and superior therapeutic efficiency [106] |
Articular cartilage defect | Human iPSCs | Differential centrifugation, ultracentrifugation (100,000× g) and ultrafiltration | EV-scaffold transplantation/1 × 1011 particles in 1 mL PBS | iPSC-EVs incorporated with in situ hydrogel glue could integrate with native cartilage matrix and promote cell deposition at cartilage defect [107] |
Osteochondral defect | BMMSCs | Ultrafiltration and sucrose gradient ultracentrifugation (100,000× g) | EV-scaffold transplantation/200 µg of total EV protein in 200 µL PBS | BMMSC-EVs together with cartilage ECM/ gelatin methacrylate hydrogel have been used to create a 3D printed device, which favoured cartilage regeneration [109] |
Kidney | ||||
AKI | Human BMMSCs | Ultracentrifugation (100,000× g) | Injection/15 µg of total EV protein | Enhanced recovery of injured tubular cells, enhanced tubular cell proliferation, reduced apoptosis [110] |
AKI (in vitro) | Human BMMSCs | Ultracentrifugation (100,000× g) | Details not provided | Increased renoprotection activity mediated by the transfer of the mRNA for IGF-1 receptor to tubular cells through the MSC-EVs [113] |
AKI | Human BMMSCs | Ultracentrifugation (100,000× g) | Injection/30 µg of total EV protein | Enhanced tubular epithelial cell proliferation, reduced cell apoptosis [114] |
AKI | Mice BMMSCs | Sequential ultracentrifugation (up to 110,000× g) | Injection/200 μg of total EV protein in 20 μL PBS | Enhanced tubular epithelial cell proliferation, reduced cell apoptosis [115] |
AKI | Human BMMSCs | Ultracentrifugation (100,000× g) | Injection/Single dose of 100 μg of total EV protein or multiple doses of 100 μg of total EV protein after cisplatin administration and 50 μg of total EV protein after 2, 6, 10, 14, and 18 days | Upregulated expression of anti-apoptotic genes in cisplatin-treated human tubular epithelial cells and down-regulated expression of cell-apoptotic genes [116] |
AKI | Mice BMMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | EV or EV-hydrogel injection/80 μg of total EV protein in 15 μL PBS or 80 μg of total EV protein in 15 μL of hydrogel solution | BMMSC-EVs loaded to self-assembling peptide nanofiber hydrogel, showed better EV efficacy and improved renal function [117] |
AKI | Human UCMSCs | Differential centrifugation and sucrose gradient centrifugation (100,000× g) | Injection/200 μg of total EV protein | Reduced oxidative stress and renal tubular cell apoptosis, increased renal cell proliferation [118] |
AKI | Human UCMSCs | Ultracentrifugation (100,000× g) | Injection/30 μg of total EV protein | Increased tubular cell proliferation and dedifferentiation [119] |
AKI | Human Wharton’s Jelly MSCs | Ultracentrifugation (100,000× g) | Injection/100 μg of total EV protein in 1 mL medium 199 | Improved renal function by enhancing tubular cell proliferation and reduced inflammation and apoptosis via mitochondrial fission [120,121] |
AKI | Human glomerular MSCs | Ultracentrifugation (100,000× g) | Injection/EVs derived from 1 × 105 cells in 120 μL PBS ((T-CD133+-EVs: 480 × 106/mouse; MSC-EVs: 400 × 106/mouse; MSC-EV-float: 400 × 106/mouse; Fibroblasts-EVs: 230 × 106/mouse) | Enhanced renal recovery [122] |
AKI | Human liver MSCs | Ultracentrifugation (100,000× g) | Injection/EVs derived from 3.5 × 105 or 10 × 105 MSCs | Enhanced renal function through increased tubular cell proliferation and inhibition of apoptosis [123] |
CDK | Human urinary MSCs | Ultracentrifugation (100,000× g) followed by sucrose gradient ultracentrifugation (100,000× g) | Injection/100 μg of total EV protein in 200 μL PBS | Reduced CKD progression by inhibiting podocyte apoptosis and promoting vascular regeneration and cell survival [125] |
CDK | Rat urinary MSCs | Total exosome isolation kit (Life Technologies) | Injection/5.3 × 107 particles in 200 μL PBS | Improved renal morphology through the anti-apoptotic behaviour of tubular epithelial cells [126] |
CDK | Human BMMSCs and human liver MSCs | Ultracentrifugation (100,000× g) | Injection/1 × 1010 particles for each injection once a week for 4 weeks (5 injections) | Reduced CDK progression through miRNAs capable of down-regulating profibrotic genes [127] |
CDK | Human liver MSCs | Sucrose gradient ultracentrifugation (350,000× g) and ultracentrifugation (100,000× g) | Injection/1 × 1010 particles in 1 mL PBS for each injection once a week for 4 weeks | Reduced CDK progression through miRNAs capable of down-regulating profibrotic genes [128] |
CDK | Mice BMMSC | Ultracentrifugation (100,000× g) | Injection/30 μg of total EV protein (3 doses) | Protected renal injury via microRNA-dependent repairing [129,130] |
CDK | Human BMMSCs | ExoQuick-TC ULTRA (EQULTRA-20TC-1, SBI) | Injection/4 × 107 particles in 2 μL PBS | Improved renal function by repairing the damage to apical and basolateral membranes and mitochondria of kidney proximal tubules [131] |
Grade III-IV CKD (clinical trial) | Human UCMSCs | Ultracentrifugation (100,000× g) | Injection/100 μg of total EV protein per kg per dose (2 doses) | Reduced the progression of CDK [132] |
Liver | ||||
Carbon tetrachloride (CCl4)-induced liver injury | Human embryonic MSCs | Tangential flow filtration and chromatography | Injection/0.4 μg of total EV protein in 100 μL PBS | Increased hepatocyte proliferation and reduced apoptosis [133] |
Hepatic ischemia-reperfusion injury | Human iPSCs | Differential centrifugation and ultrafiltration | Injection/600 μg of total EV protein in 400 μL PBS | Enhanced hepatic regeneration via inhibition of apoptosis of hepatic cells, suppression of inflammatory and attenuation of the oxidative stress response [134] |
Hepatic ischemia-reperfusion injury | Human iPSCs | ExoQuick Exosome Precipitation Solution (SBI Systems Biosciences) | Injection/2.5 × 1012 particles in 500 μL PBS | Increased hepatocyte proliferation in vitro and in vivo in a dose-dependent manner [135] |
Hepatic ischemia-reperfusion injury | Human UCMSCs | Ultracentrifugation (100,000× g) | Injection/10 mg of total EV protein per kg | Reduced infiltration of neutrophils and oxidative stress in hepatic tissue [139] |
Chronic hepatic fibrosis | Human embryonic MSCs | Differential centrifugation and ultracentrifugation (100,000× g) | EV-hydrogel injection/350 μg of total EV protein in 400 μL PEG hydrogel solution | Sustained release of MSC-EVs from PEG hydrogels protected against hepatic failure [140] |
Muscle | ||||
Cardiotoxin-induced muscle injury | Human BMMSCs | Sequential ultracentrifugation (110,000× g) | Injection/details not provided | Enhanced muscle regeneration through increased myogenesis and angiogenesis [141] |
Cardiotoxin-induced muscle injury | Human amniotic fluid MSCs | Ultracentrifugation (200,000× g) | Injection/details not provided | Enhanced muscle regeneration through regulation of inflammation and angiogenesis [142] |
Tibialis anterior muscle damage | Human ADMSCs | Ultracentrifugation (200,000× g) | Injection/EVs derived from 1 × 106 cells | Enhanced muscle regeneration through the synergistic effect of EVs and soluble proteins [143] |
Muscle degeneration associated to torn rotator cuffs | Human ADMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/1 × 1011 particles in 20 μL PBS | Enhanced myofiber regeneration and biomechanical properties of muscles in rotator cuffs [144] |
Pubococcygeus muscle injury | Human urine-derived MSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/1 × 1010 particles in 1 mL PBS | Enhanced muscle regeneration through the activation, proliferation, and differentiation of muscle satellite cells [145] |
Muscle damage associated to critical limb ischemia | Human ADMSCs | Ultracentrifugation (100,000× g) | Injection/1 × 1010 particles intravenously or intramuscularly after intervention, 0.5 × 1010 via intramuscular injection after day 1 and 2 | Enhanced muscle regeneration/protection through NRG1-mediated signals [146] |
Wounds | ||||
Fibroblasts from normal and chronic wound patients (in vitro) | Human BMMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | 0.1, 1, and 10 μg total EV protein in 1 mL PBS | Enhanced proliferation and migration of fibroblasts and tube formation by endothelial cells [149] |
Skin wound | Human iPSC | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/160 μg total EV protein in 160 μL PBS at wound sites and 40 μg total EV protein in 40 μL PBS at wound beds | Increased collagen synthesis and angiogenesis [150] |
Photo-damaged dermal fibroblasts in vitro) | Human ADMSCs | Tangential flow filtration | 1 × 108 particles in 1 mL PBS | Increased collagen and elastin synthesis and decreased metalloproteinases activity [151] |
Skin wound | Human ADMSCs | Ultrafiltration and ExoQuick-TC kit (System Biosciences) | Injection/200 μg of total EV protein in 200 μL PBS | Enhanced wound healing by regulating the collagen distribution secreted by fibroblasts in the early and late stage of wound healing [152] |
Excisional skin wound | Human ADMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | EV-gel transplantation/1.9 × 108 particles in hydroxyethyl cellulose aqueous gel | Enhanced wound healing through increased migration and proliferation of keratinocytes and fibroblasts [153] |
Ischemic wound | Human ADMSCs | ExoQuick-TC kit (System Biosciences) | Injection/details not provided | Enhanced wound healing through migration and proliferation of dermal fibroblasts [154] |
Cutaneous wound | Rabbit ADMSCs and BMMSCs | Ultracentrifugation (100,000× g) | Injection/EVs derived from 10 × 106 MSCs | Significant better wound healing upon treatment with ADMSC-EVs [155] |
Second-degree burn wound | Human UCMSCs | Differential centrifugation and sucrose gradient ultracentrifugation (100,000× g) | Injection/200 μg of total EV protein in 200 μL PBS | Enhanced wound healing through increased fibroblasts proliferation and angiogenesis and reduced skin cell apoptosis [156,157,158] |
Skin wound | Human UCMSCs | Differential centrifugation and ultracentrifugation (120,000× g) | EV-scaffold transplantation/100 μg of total EV protein in 100 μL PBS | Enhanced wound healing and reduced scar formation through inhibition of myofibroblast differentiation [159] |
Other tissues/organs | ||||
Injuries in lung cells (in vitro) | Human placenta MSC | Differential centrifugation and ultracentrifugation (100,000× g) | 6 × 105 particles in 20 µL serum-free media | Enhanced cell migration, reduced oxidative cell stress and inflammation [160] |
Influenza virus-induced acute lung injury | Swine BMMSCs | Ultracentrifugation (25,000 rpm) | Intratracheally/EVs produced by 10 × 106 MSCs | Reduced virus shedding, production of proinflammatory cytokines, and influenza virus-induced lung lesions [161] |
lung injury induced by haemorrhagic shock and trauma | Human BMMSs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/30 μg of total EV protein in 200 μL PBS | Improved pulmonary vascular permeability through the activation of proteins and pathways linked to cytoskeletal rearrangement [162] |
Hyperlipidaemia | Human placenta MSC | Differential centrifugation and ultracentrifugation (100,000× g) | EV-scaffold transplantation/100 μg of total EV protein in 1 mL PBS | Reduced calcification of synthetic vascular grafts by immunomodulation and improved vascular function [163] |
Neointimal hyperplasia (in vitro) | Human ADMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | 100 μg of total EV protein in 1 mL PBS | Reduced abnormal proliferation and migration of vascular smooth muscle cell [164] |
Hind-limb ischemia | Human UCMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/2 × 1010 particles in 1 mL PBS | Enhanced angiogenesis and muscle regeneration, and ischemic limp function [165] |
Tracheoesophageal fistulas | Porcine ADMSCs | Ultracentrifugation (100,000× g) | EV-gel injection/1.3 × 1011 particles in 1 ml of pluronic F127 gel | Enhanced oesophageal fistula healing through targeted delivery of EVs embedded in thermo-responsive hydrogels [166] |
Ulcerative colitis | Mouse BMMSCs | Differential centrifugation and ultracentrifugation (100,000× g) | Injection/50 μg of total EV protein per day for 7 days | Improved symptoms through stimulating M2 macrophage polarization and negative inflammatory response [167] |
Tissue Injury/Disease | Condition | Treatment | Trial Phase | Trial ID |
---|---|---|---|---|
Lung injury | Healthy | Aerosol inhalation of allogenic ADMSC-EVs (2 × 108 particles/3 ml or 1 × 108 particles/3 ml) | Phase I | NCT04313647 |
Lung disease (pneumonia) | Coronavirus disease-19 | Aerosol inhalation of allogenic ADMSC-EVs (2 × 108 particles/3 ml) for 5 days | Phase I | NCT04276987 |
Chronic lung disease | Bronchopulmonary dysplasia | Intravenous infusion of BMMSC-EVs (20 or 60 or 200 pmol phospholid/kg body weight) | Phase I | NCT03857841 |
Cartilage injury | Osteoarthritis | Osteochondral explants from arthroplasty patients treated with ADMSC-EVs | Phase I | NCT04223622 |
Brain injury | Acute ischemic stroke | Administration of allogenic MSC-EVs enriched with miR-124 (200 μg total EV protein) via Stereotaxis | Phase II | NCT03384433 |
Skin injury | Dystrophic Epidermolysis Bullosa | Allogenic BMMSC-EVs locally administrated | Phase II | NCT04173650 |
Kidney disease | CDK | Injection of allogenic UMMSC-EVS (100 μg of total EV protein per kg per dose) | Phase II/III (completed) | [132] |
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Tsiapalis, D.; O’Driscoll, L. Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells 2020, 9, 991. https://0-doi-org.brum.beds.ac.uk/10.3390/cells9040991
Tsiapalis D, O’Driscoll L. Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells. 2020; 9(4):991. https://0-doi-org.brum.beds.ac.uk/10.3390/cells9040991
Chicago/Turabian StyleTsiapalis, Dimitrios, and Lorraine O’Driscoll. 2020. "Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications" Cells 9, no. 4: 991. https://0-doi-org.brum.beds.ac.uk/10.3390/cells9040991