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 BMMSCsversus 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. Thetherapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistryfor liver fibrosis and hepatocellular injury.

RESULTS:Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression ofcollagen 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 andhepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuatinghepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-freetherapeutic strategy for liver fibrosis and hepatocellular damage.