Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases
Abstract
:1. Introduction
2. Biogenesis and General Physiological Functions of Exosomes
3. Contents and Physiological Functions of MSC-Derived Exosomes
4. Therapeutic Applications and Mechanisms of MSC-Derived Exosomes in Liver Diseases
4.1. MSC-Derived Exosomes for the Treatment of Liver Injury
4.2. MSC-Derived Exosomes for the Treatment of Liver Fibrosis
4.3. MSC-Derived Exosomes for the Treatment of Acute Liver Failure
4.4. MSC-Derived Exosomes for the Treatment of Hepatocellular Carcinoma
5. Clinical Trials Using MSCs for the Treatment of Liver Diseases
6. MSC-Derived Exosomes: A Double-Edged Sword for Disease Treatment
7. Current Challenges
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Diseases | Source of MSCs | Injection Route | Test Evaluation Subjects | Phase | ClinicalTrials.gov Identifier |
---|---|---|---|---|---|
HBV-related acute-on-chronic liver failure | UCB-MSCs | Peripheral veins | Safety and efficacy | Phase II | NCT02812121 |
Liver failure caused by hepatitis B | Autologous MMSCs | The proper hepatic artery | The short-term efficacy and long-term prognosis | Unknown | NCT00956891 |
Acute-on-chronic liver failure caused by HBV | HUC-MSCs | Peripheral vein | Safety and efficacy | Phase I/II | NCT01724398 |
HBV-related liver failure | Allogeneic HBM-MSCs and HUC-MSCs | Peripheral vein | Safety and efficacy | Phase I/II | NCT01844063 |
The early and middle stage of liver cirrhosis on the basis of HBV infection | Autologous BMSCs | Portal vein | The therapeutic efficacy | Phase II | NCT00993941 |
HBV-related liver cirrhosis | Autologous BMSCs | Hepatic artery | Safety and efficacy | Phase I/II | NCT01724697 |
Liver cirrhosis resulting from chronic HBV | Allogenic BMSCs | Portal vein or hepatic artery | The therapeutic efficacy | Phase II | NCT01223664 |
Liver cirrhosis with refractory ascites | Autologous BMSCs | Liver artery | The effect of MSCs in the patients | Phase III | NCT01854125 |
Alcoholic liver cirrhosis | BMSCs | Hepatic artery catheterizations | Safety and efficacy | Phase II | NCT01741090 |
Liver cirrhosis | UC-MSCs | Intravenously | Safety and efficacy | Phase I/II | NCT01220492 |
Decompensated cirrhosis | HUC-MSCs | Intravenously | Safety and efficacy | Phase II | NCT05224960 |
Liver cirrhosis due to biliary atresia | UC-MSCs | Hepatic artery | Safety and efficacy | Phase I/II | NCT04522869 |
Liver cirrhosis | UC-MSCs | Hepatic artery | Safety and efficacy | Phase I/II | NCT01224327 |
Liver cirrhosis | UC-MSCs | Hepatic artery and intravenously | The efficacy of different interventional therapies | Phase I/II | NCT01233102 |
Source of Exosomes | Study Purposes | Study Results | References |
---|---|---|---|
Human BMSC-derived exosomes | To study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells | Promoting MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway | [116] |
BMSC-derived exosomes | To explore the impact of the miR-208a-enriched exosomes derived from BMSCs on osteosarcoma cells. | Promoting proliferation, migration and invasion of osteosarcoma cells partly through downregulation of PDCD4 and activation of ERK1/2 pathway | [117] |
Adult BMSC-derived exosomes | To explore the role of BMSC-derived exosomes mediating miR-19b-3p in EC cell growth | BMSC-derived exosomal microRNA-19b-3p targets SOCS1 to facilitate progression of esophageal cancer | [118] |
Hypoxic BMSC-derived exosomes | To further elucidate the communication between BMSC-derived exosomes and cancer cells in the hypoxic niche | Exosome-mediated transfer of miR-193a-3p, miR-210-3p and miR-5100, could promote invasion of lung cancer cells by activating STAT3 signaling-induced EMT | [119] |
Exosomes derived from gastric cancer tissue-derived MSCs | To explore the expression and role of miRNAs in gastric cancer stromal cells | Favouring gastric cancer progression by transferring exosomal miRNAs to gastric cancer cells | [120] |
Human BMSC-derived exosomes | To explore the mechanism of MSCs xenograft promoting tumor growth | Enhancing VEGF expression in tumor cells by activating ERK1/2 pathway to promote tumor growth in vivo | [121] |
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Ding, Y.; Luo, Q.; Que, H.; Wang, N.; Gong, P.; Gu, J. Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases. Int. J. Mol. Sci. 2022, 23, 10972. https://doi.org/10.3390/ijms231810972
Ding Y, Luo Q, Que H, Wang N, Gong P, Gu J. Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases. International Journal of Molecular Sciences. 2022; 23(18):10972. https://doi.org/10.3390/ijms231810972
Chicago/Turabian StyleDing, Yi, Qiulin Luo, Hanyun Que, Nan Wang, Puyang Gong, and Jian Gu. 2022. "Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases" International Journal of Molecular Sciences 23, no. 18: 10972. https://doi.org/10.3390/ijms231810972