Could Mesenchymal Stem Cell-Derived Exosomes Be a Therapeutic Option for Critically Ill COVID-19 Patients?
Abstract
:1. Introduction
2. SARS-CoV-2, the Angiotensin-Converting Enzyme 2 Receptor and the Renin-Angiotensin System
3. Anti-Inflammatory and Immunomodulatory Properties of MSCs and MSC Secretome
3.1. MSC-Derived EVs as a Therapeutic Pption for Critically Ill COVID-19 Patients
3.2. MSC-Derived EVs from Patients with Metabolic Disorders
4. Pre-Clinical Evidence on the Use of MSC-Derived Exosomes in Animal Models of Lung and Heart Injuries
4.1. MSC-Derived Exosomes and Respiratory Lung Injuries
4.2. MSC-Derived Exosomes and Heart Injuries
5. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Disease | Model | EV 1 Origin | EV Administration Route and Dosage | Main Findings | Reference |
---|---|---|---|---|---|
ALI 2 | IT 3 instillation of Escherichia coli endotoxin (4 mg/kg) in C57BL/mice | MSCs from human bone marrow | IT or IV 4 administration of 30 μL (3 × 106 cell equivalents) of MVs 5 simultaneously to endotoxin inoculation |
| [101] |
ALI | IT instillation of LPS 10 (4 mg/kg) from Pseudomonas aeruginosa in C57BL/mice | MSCs from human bone marrow | IT administration of 30 μL (3 × 106 cell equivalents) of MVs simultaneously to endotoxin inoculation |
| [105] |
ALI | intranasal instillation of LPS (20 mg/kg) from Escherichia coli in C57BL/mice | MSCs from human bone marrow | intranasal administration of AM 12 (2.5 × 105 cells/mouse) pre-treated ex vivo with MSC-derived EVs 4 h after endotoxin inoculation |
| [111] |
ALI | IT instillation of Escherichia coli K1 strain (2 or 3 × 106 cfu 14) in C57BL/mice | MSCs from human bone marrow | IV administration of 90 uL (9 × 106 cell equivalents) of MVs 4 h after bacterial inoculation |
| [114] |
ALI | HLMVECs 16 injured by cytomix (50 ng/mL of IL-1β, TNF-α, and IFN-γ) | MSCs from human bone marrow | 30 or 60 uL of MVs (10 uL corresponding to MVs released by 1 × 106 MSCs) simultaneously to cytomix treatment |
| [116] |
ARDS 17 | intranasal inoculation of swine influenza virus (5 × 106 TCID50 18/pig) in White-Duroc crossbred pigs | MSCs from swine bone marrow | IT administration of EVs (80 µg/kg) 12 h after viral infection |
| [118] |
Disease | Model | EVs Origin | EVs Administration Route and Dosage | Main Findings | Reference |
---|---|---|---|---|---|
I/R 1 injury | 30 min ischemia through ligation of LCA 2 in C57BL/6J mice followed by 24 h reperfusion | MSCs from HuES9.E1 cells | IV 3 injection of 0.4 µg/mL of exosomes, 5 min before reperfusion |
| [139] |
AMI 6 | permanent ligation of LAD 7 coronary artery in Wistar rats | MSCs from human bone marrow | Four intramyocardial injections of 80 µg of EVs (2 × 106 cell equivalents) from hypoxic- and serum-deprivated MSCs, 30 min after ligation |
| [140] |
AMI | permanent ligation of LAD coronary artery in Sprague-Dawley rats | MSCs from human umbilical cord | IV injection of 400 µg of exosomes from Akt-transfected MSCs, immediately after ligation |
| [141] |
AMI | permanent ligation of LAD coronary artery in C57/B6 mice | MSCs from mice heart | intramyocardial injection of 20 µL of EVs (1 × 1012 particles/mL), 10 min after ligation |
| [142] |
AMI | permanent ligation of LAD coronary artery in Sprague-Dawley rats | MSCs from rat bone marrow | intramyocardial injection of 80 µg of exosomes, 60 min after ligation |
| [144] |
AMI | permanent ligation of LAD coronary artery in C57BL/6J mice | MSCs from mouse bone marrow | intramyocardial injection of 1 µg of exosomes from ischemic pre-conditioned MSCs, immediately after ligation |
| [145] |
AMI | permanent ligation of LAD coronary artery in Sprague-Dawley rats | MSCs from human umbilical cord | IV injection of 400 µg of exosomes, immediately after ligation |
| [146] |
AMI | permanent ligation of LAD coronary artery in Sprague-Dawley rats | MSCs from rat bone marrow | intramyocardial injection of 50 µL of exosomes from GATA-4 over-expressing MSCs (4 × 106 cells), immediately after ligation |
| [147] |
AMI | permanent ligation of LAD coronary artery in Sprague-Dawley rats | MSCs from rat bone marrow | intramyocardial injection of 20 µg (in 20 µL of PBS 13) of exosomes, immediately after ligation |
| [148] |
I/R injury | 30 min ischemia through ligation of LCA in Sprague-Dawley rats followed by 2 h reperfusion | MSCs from rat bone marrow | intramyocardial injection of 5 µg (in 10 µL of PBS) of exosomes, 5 min before reperfusion |
| [151] |
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Gardin, C.; Ferroni, L.; Chachques, J.C.; Zavan, B. Could Mesenchymal Stem Cell-Derived Exosomes Be a Therapeutic Option for Critically Ill COVID-19 Patients? J. Clin. Med. 2020, 9, 2762. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092762
Gardin C, Ferroni L, Chachques JC, Zavan B. Could Mesenchymal Stem Cell-Derived Exosomes Be a Therapeutic Option for Critically Ill COVID-19 Patients? Journal of Clinical Medicine. 2020; 9(9):2762. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092762
Chicago/Turabian StyleGardin, Chiara, Letizia Ferroni, Juan Carlos Chachques, and Barbara Zavan. 2020. "Could Mesenchymal Stem Cell-Derived Exosomes Be a Therapeutic Option for Critically Ill COVID-19 Patients?" Journal of Clinical Medicine 9, no. 9: 2762. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092762