Extracellular vesicle mimetics engineered from mesenchymal stem cells and curcumin promote fibrosis regression in a mouse model of thioacetamide-induced liver fibrosis

Abstract

Recent research suggests that advanced liver fibrosis could be reversed, but the therapeutic agents needed for the prevention of liver fibrosis remain to be elucidated. The beneficial effects of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) on liver fibrosis have been reported. However, the large-scale production of MSC-EVs remains challenging. The present study investigated the therapeutic effects of mouse MSC-derived EV mimetics (MEVMs) in combination with curcumin (antifibrotic compound) using a mouse model of thioacetamide-induced liver fibrosis. MEVMs were prepared through the serial extrusion of MSCs. These MEVMs were similar in size and morphology to the EVs. The biodistribution study showed that fluorescently labeled MEVMs predominantly accumulated in the liver. The establishment of liver fibrosis was confirmed via increased collagen (histology), liver fibrosis score, α-smooth muscle actin (α-SMA), and vimentin proteins levels. Treatment with MEVMs, curcumin, or their combination decreased the amount of collagen in liver tissues, with the antifibrotic effects of MEVMs being further confirmed by the liver fibrosis score. All treatments decreased the expression of collagen 1α, α-SMA, and vimentin. MEVMs showed superior effects than curcumin. Thus, MSC-derived EVMs could be a potential alternative for the treatment of liver fibrosis.

Keywords

• Extracellular vesicles-mimetics
• Mesenchymal stem cells
• Liver fibrosis
• Curcumin