Poster Presentation Australasia Extracellular Vesicles Conference 2017

Human amnion epithelial cells-derived extracellular vesicles reduce fibrosis in a mouse model of liver fibrosis. (#57)

Majid Alhomrani 1 2 3 , Jeanne Correia 1 , Alex Hodge 1 2 , Rebecca Lim 4 5 , William Sievert 1 2 , Bryan Leaw 6
  1. Centre for Inflammatory Disease, Monash University, Clayton, VIC, Australia
  2. Gastroenterology and Hepatology Unit, Monash Medical Centre, Clayton, VIC, Australia
  3. Medical College, Taif University, Taif, Saudi Arabia
  4. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia
  5. Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, Australia
  6. Hudson Institute of Medical Research, Clayton, VIC, Australia

Background: Hepatic stellate cells (HSCs) are the primary collagen-secreting cells in the liver and the major cell type involved in liver fibrosis. We observed a reduction in activation, proliferation and collagen synthesis in HSCs exposed to human amnion epithelial cells (hAEC) and hAEC conditioned media. This suggested that the secretome of hAEC may be effective in ameliorating liver fibrosis. Extracellular vesicles (EVs) are secreted nanosized (40-100 nm) membrane vesicles that may act as a novel cell-cell communicator. We investigated the efficacy of hAEC-EVs in a mouse model of chronic liver fibrosis and in human HSC.

Methods: EVs were isolated from conditioned media using ultracentrifugation and characterised by electron microscopy. LX-2 cells, a human HSCs line, were exposed to EVs (1μg, 5μg and 10μg). Collagen synthesis was assessed using [3H]-proline incorporation. Mice given CCl4 for 12 weeks were treated intravenously with EVs 1μg 3 times/week for the last 4 weeks of the model. Liver fibrosis was determined by Sirius red staining, HSCs activation was determined by staining with α-SMA and hepatic macrophages were identified by F4/80 staining.

Results: HSCs treated for 48 hours with EVs 10μg displayed a significant reduction in collagen synthesis (P<0.0001). In treated mice, hepatic fibrosis area and HSCs numbers were reduced significantly in mice given EVs (p<0.0001) compared to untreated controls. Hepatic macrophages were significantly decreased in treatment groups (p<0.0001).

Conclusion: hAEC-EVs significantly reduced liver fibrosis and macrophage infiltration in vitro and in vivo. hAEC-EVs based therapy appears promising for patients with chronic liver disease.