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

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. 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. 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. 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.