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The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

The extracellular vesicles (EVs) secreted by bone marrow-derived mesenchymal stem cells (MSCs) hold significant potential as a novel alternative to whole-cell therapy. We herein compare the therapeutic potential of BM-MSCs versus their EVs (MSC-EVs) in an experimental Carbon tetrachloride (CCl4)-induced liver damage rat model.

Methods:

Rats with liver damage received a single IV injection of MSC-EVs, 1 million MSCs, or 3 million MSCs. The therapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistry for liver fibrosis and hepatocellular injury.

Results:

Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression of collagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and functionally.

Conclusion:

Similar to high doses of MSC-based therapy (3 million MSCs), MSC-EVs mitigated the fibrogenesis and hepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuating hepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-free therapeutic strategy for liver fibrosis and hepatocellular damage.

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Acknowledgements

Acknowledgements Authors acknowledge the technical help at the Center of Excellence for Research in Regenerative Medicine Applications (CERRMA), Alexandria Faculty of Medicine. DMR and NA carried out the experimental work, Designed the experiments and co-wrote the manuscript. HMK and MWAN shared in experimental design, performed the analytical part of the study, supervised the research and revised the manuscript EAES optimized the design of experiments, supervised the research, gave conceptual advice. All authors read and approved the manuscript.

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Correspondence to Noha Attia.

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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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The animal studies were performed after receiving approval of the institutional review board of ethics (618/5020/2016), Faculty of medicine, University of Alexandria.

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Rostom, D.M., Attia, N., Khalifa, H.M. et al. The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage. Tissue Eng Regen Med 17, 537–552 (2020). https://doi.org/10.1007/s13770-020-00267-3

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