Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine: A Comprehensive Review
Abstract
:1. Introduction
2. A Biological and Mechanistic Approach to Confer the Potential of Exosomes: A General Account
2.1. Biogenesis of Exosomes
2.2. Exosome Secretion and Internalization
2.3. Isolation of Exosomes: The First Step towards Pharmaceuticalization
2.4. Characterization and Visualization of Exosomes
3. The Therapeutic Nature of MSC Derived Exosomes by the Synergistic Functioning of miRNAs and Proteins
4. Therapeutic Potential of MSC Derived Exosomes in Various Diseases
4.1. MSC Derived Exosomes in Cardiovascular Diseases
4.2. MSC Derived Exosomes in Neurodegenerative Diseases
4.3. MSC Derived Exosomes in Kidney Diseases
4.4. MSC Derived Exosomes in Liver Diseases
4.5. MSC Derived Exosomes in Cancer
4.6. MSC Derived Exosomes in Lung Diseases
MSC Derived Exosomes in COVID-19
5. Exosomes as a Drug Delivery Vehicle
6. Limitations and Leads for the Future
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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MSCs | MSC Exosomes |
---|---|
Low stability | High Stability |
High immunogenicity | Low immunogenicity |
Cannot cross blood brain barrier | Can easily cross blood brain barrier |
High-cost storage | Low-cost storage |
Can-not be readily used as off-the-shelf | Potential for off-the-shelf availability |
Disease | Cell Source | Exosome Content | Mechanism of Action | Reference |
---|---|---|---|---|
Myocardial ischemia/reperfusion injury | hESC derived MSC | Not given | Out of the complex mixture of nutrients, growth factors, microvesicles etc. in the conditioned media, exosomes are specifically responsible for tissue repair and cardioprotective effects in case of ischemia/reperfusion injury | [68] |
Acute Myocardial Infarction | hESC derived MSC | Peroxiredoxins and glutathione S-transferase, enzymatically active CD73 | Increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β | [69] |
Myocardial Infarction | hBMMSC | Sonic hedgehog, PDGFR | Increased angiogenesis, HIF-1 alpha activation | [70] |
Ischemic heart | Mice BMMSC | miR22 | Targeting the methyl CpG binding protein 2 (Mecp2) | [71] |
Myocardial Infarction | MSC overexpressing GATA-4 | miR-19a, miR-451, miR-221, IGF-1 | Anti-apoptotic effect, reduction in PTEN and BIM expression, Akt/ERK signalling pathway | [72] |
Myocardial Infarction | Human Endometrium-derived MSC (EnMSC) | miR-21 | PTEN/Akt pathway | [73] |
Acute Myocardial Infarction | Atorvastatin treated MSC | lncRNA H19 | Increased angiogenesis, inhibited the elevation of IL-6 and TNF-α | [74] |
H9C2 cardiomyocyte | Mice BMMSC | miR-144 | PTEN/Akt pathway | [75] |
Myocardial Infarction | Mice BMMSC | miR-210 | Reduce apoptosis of cardiomyocytes, AIFM3/p53 and PI3K/Akt signaling pathways | [76] |
Stroke | Rat BMMSC | miR-133b | Enhanced neurological recovery, stimulated neurogenesis and angiogenesis | [77] |
Stroke | hBMMSC | Not given | Stimulated neurogenesis and angiogenesis | [78] |
Parkinson’s disease | Human dental pulp stem cells | Not given | Suppressed 6-OHDA-induced apoptosis in dopaminergic neurons | [82] |
Age-related macular degeneration | Retinal pigment epithelial cells | αB crystallin | Inhibition of caspase 3 and PARP activation | [84] |
Parkinson’s disease | Mouse macrophage cell line | Catalase | Reduced Oxidative stress | [85] |
Alzheimer’s disease | hADMSC | Neprilysin | β-amyloid peptide degradation | [86] |
SH-SY 5Y human neuroblastoma cells | murineADMSC | Not given | Reduction of neuronal apoptosis | [88] |
Amyotrophic lateral sclerosis | murineADMSC | miR21, miR222, miRlet7a | Apoptosis-inhibiting pathway, cell cycle progression | [87] |
Acute kidney injury | hBMMSC | IGF-1R | Increased proximal renal tubular epithelial cell proliferation | [92] |
Acute kidney injury | hBMMSC | mRNA | Induced de-differentiation of mature cells, triggered proliferation | [93] |
Acute kidney injury | hMSC | Not given | Upregulated anti-apoptotic genes Bcl-xL, Bcl2 and BIRC8 in tubular epithelial cells | [96] |
Renal proximal tubular epithelial cells | hBMMSC | let7- a, miR-148b-3p, 375, 410, 451, 485-3p, 495, 522, 548c-3p, 548c-5p, 561, and 886-3p | Downregulation of apoptotic genes, SHC1 mediated inhibition of EGFR-Ras-ERK pathway | [97] |
Renal ischemia/reperfusion injury | hWJMSC | Not given | Supress expression of NOX2, ROS level reduction | [98] |
Renal ischemia/reperfusion injury | hWJMSC | miR-15a, miR-15b and miR-16 | Downregulation of CX3CL1 | [99] |
Chronic kidney disease | hCBMSC | Not given | Increase in TGF-β1 and IL-10 levels, decrease in TNF-α levels | [100] |
Chronic liver fibrosis | murineBMMSC | Not given | Inhibition of hepatocellular apoptosis, inhibition of proliferation of LX-2 | [98] |
Liver fibrosis | hUCMSC | Not given | Inhibition of EMT, inactivation of the TGF-β1/Smad signalling | [103] |
Liver fibrosis | chorionic plate-derived mesenchymal stem cells (CP-MSCs) | miR-125b | Downregulation of hedgehog signaling | [104] |
Liver fibrosis | ADMSC | miR-122 | proliferation and collagen maturation of HSCs | [106] |
Liver Injury | hESC-derived HuES9.E1 MSC | Not given | Up regulation of PCNA and cyclin D1, inhibition of the APAP- and H2O2-induced hepatocytes apoptosis | [107] |
Acute liver Injury | hUC-MSC | miR-455-3p | PI3K signaling, inhibition of IL-6-related signaling pathways, suppress monocyte/macrophage activation | [108] |
Acute liver failure | miceADMSC | miR-17 | Suppress NLRP3 inflammasome activation | [109] |
Prostate cancer | hADMSC | miR-145 | Inhibit cell proliferation, inducing apoptosis | [113] |
Multiple Myeloma | hBMMSC | miR-15a | Inhibited the growth of MM cells | [114] |
Renal cancer | hWJMSC | HGF mRNA | Activation of AKT and ERK1/2 signaling pathways, reduction of HGF expression | [115] |
Human gastric carcinoma | hBMMSC | VEGF | Inhibition of ERK1/2 activation | [116] |
Nasopharyngeal carcinoma | hBMMSC | FGF19 | FGF19-FGFR4-dependent ERK signaling | [117] |
Breast cancer cell line (MCF-7) | hSDMSC | miR-21, miR-34a, PDGFR-β, TIMP-1, and TIMP-2, sphingomyelin, lactic acid, glutamic acid | Inhibited cell death, anti-proliferative effect | [118] |
Osteosarcoma (MG63) and gastric cancer (SGC7901) cells | hBMMSC | Not given | Hedgehog signaling pathway | [120] |
Mouse breast cancer cell line (4T1) | miceBMMSC | miR-16 | Inhibition of tumor growth and angiogenesis, reduces the VEGF expression | [121] |
Prostate Adenocarcinoma PC3 | Menstrual MSC | Not given | Reduction in VEGF secretion and NF-κB activity, lower ROS | [122] |
Hepatocellular carcinoma | ratADMSC | β-catenin | Promoted NKT-cell antitumor responses, low-grade tumor differentiation | [123] |
Glioblastoma multiforme | hBMMSC | anti-miR-9 | Reduced miR-9, cell surface P-gp | [125] |
Hepatocellular carcinoma | miR-122-modified AD-MSC | miR-122 | Enhancing cell sensitivity to chemotherapeutic agents | [106] |
Acute lung injury by Influenza virus | Swine BMMSC | Cyclooxygenase (COX)-2 mRNA, Indoleamine 2,3-dioxygenase (IDO) | Reduce Haemagglutination activity of influenza viruses, virus replication, decrease in proinflammatory cytokine production | [131] |
LPS induced Acute lung injury | BMMSC overexpressing miR-30b-3p | miR-30b-3p | Decreased SAA3 level, increased cell proliferation, reduce apoptosis | [132] |
Lung Ischemia/Reperfusion injury | Murine BMMSC | miR-21-5p | Reduced lung edema and dysfunction, M1 polarization of alveolar macrophages, increase secretion of HMGB1, IL-8, IL-1β, IL-6, IL-17 and TNF-α | [133] |
E. coli-induced acute lung injury | hUCMSC | hsp-90 | Reduced alveolar protein leak, increased lung mononuclear phagocytes, reduced alveolar tumor necrosis factor alpha concentrations | [134] |
E. coli induced acute lung injury | hBMMSC | Not given | Decrease in lung protein permeability, increased alveolar fluid clearance, antimicrobial effect | [135] |
Acute lung injury due to severe pneumonia (E. coli induced) | hBMMSC | Not given | Reduced inflammation, total bacterial load, lung protein permeability, increase monocyte phagocytosis, Restored intracellular ATP levels in injured human ATII cells | [136] |
COVID-19 | hMSC (UCMSC, BMMSC, ADMSC, dental pulp MSC) | Not given | Inhibit macrophage accumulation and activation, cytokine strome reduction, reduction in CD4+ T cells, CD8+ T cells | [137] |
COVID-19 | BMMSC | ExoFlo™ | Improved oxygenation, improvements in absolute neutrophil count, C-reactive protein, ferritin, and D-dimer reduction | [145] |
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Panda, B.; Sharma, Y.; Gupta, S.; Mohanty, S. Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine: A Comprehensive Review. Life 2021, 11, 784. https://doi.org/10.3390/life11080784
Panda B, Sharma Y, Gupta S, Mohanty S. Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine: A Comprehensive Review. Life. 2021; 11(8):784. https://doi.org/10.3390/life11080784
Chicago/Turabian StylePanda, Biswajit, Yashvi Sharma, Suchi Gupta, and Sujata Mohanty. 2021. "Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine: A Comprehensive Review" Life 11, no. 8: 784. https://doi.org/10.3390/life11080784
APA StylePanda, B., Sharma, Y., Gupta, S., & Mohanty, S. (2021). Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine: A Comprehensive Review. Life, 11(8), 784. https://doi.org/10.3390/life11080784