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The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis

Overview of attention for article published in Frontiers in Pharmacology, October 2017
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Title
The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis
Published in
Frontiers in Pharmacology, October 2017
DOI 10.3389/fphar.2017.00748
Pubmed ID
Authors

Majid Alhomrani, Jeanne Correia, Marcus Zavou, Bryan Leaw, Nathan Kuk, Rong Xu, Mohamed I. Saad, Alexander Hodge, David W. Greening, Rebecca Lim, William Sievert

Abstract

Background: Hepatic stellate cells (HSCs) are the primary collagen-secreting cells in the liver. While HSCs are the major cell type involved in the pathogenesis of liver fibrosis, hepatic macrophages also play an important role in mediating fibrogenesis and fibrosis resolution. Previously, we observed a reduction in HSC activation, proliferation, and collagen synthesis following exposure to human amnion epithelial cells (hAEC) and hAEC-conditioned media (hAEC-CM). This suggested that specific factors secreted by hAEC might be effective in ameliorating liver fibrosis. hAEC-derived extracellular vesicles (hAEC-EVs), which are nanosized (40-100 nm) membrane bound vesicles, may act as novel cell-cell communicators. Accordingly, we evaluated the efficacy of hAEC-EV in modulating liver fibrosis in a mouse model of chronic liver fibrosis and in human HSC. Methods: The hAEC-EVs were isolated and characterized. C57BL/6 mice with CCl4-induced liver fibrosis were administered hAEC-EV, hAEC-CM, or hAEC-EV depleted medium (hAEC-EVDM). LX2 cells, a human HSC line, and bone marrow-derived mouse macrophages were exposed to hAEC-EV, hAEC-CM, and hAEC-EVDM. Mass spectrometry was used to examine the proteome profile of each preparation. Results: The extent of liver fibrosis and number of activated HSCs were reduced significantly in CCl4-treated mice given hAEC-EVs, hAEC-CM, and hAEC EVDM compared to untreated controls. Hepatic macrophages were significantly decreased in all treatment groups, where a predominant M2 phenotype was observed. Human HSCs cultured with hAEC-EV and hAEC-CM displayed a significant reduction in collagen synthesis and hAEC-EV, hAEC-CM, and hAEC-EVDM altered macrophage polarization in bone marrow-derived mouse macrophages. Proteome analysis showed that 164 proteins were unique to hAEC-EV in comparison to hAEC-CM and hAEC-EVDM, and 51 proteins were co-identified components with the hAEC-EV fraction. Conclusion: This study provides novel data showing that hAEC-derived EVs significantly reduced liver fibrosis and macrophage infiltration to an extent similar to hAEC-EVDM and hAEC-CM. hAEC-EV-based therapy may be a potential therapeutic option for liver fibrosis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 53 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 19%
Researcher 7 13%
Student > Doctoral Student 4 8%
Student > Master 4 8%
Student > Bachelor 4 8%
Other 5 9%
Unknown 19 36%
Readers by discipline Count As %
Medicine and Dentistry 9 17%
Biochemistry, Genetics and Molecular Biology 8 15%
Agricultural and Biological Sciences 5 9%
Immunology and Microbiology 4 8%
Engineering 3 6%
Other 3 6%
Unknown 21 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 October 2017.
All research outputs
#20,450,513
of 23,006,268 outputs
Outputs from Frontiers in Pharmacology
#10,211
of 16,313 outputs
Outputs of similar age
#285,594
of 327,740 outputs
Outputs of similar age from Frontiers in Pharmacology
#168
of 276 outputs
Altmetric has tracked 23,006,268 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,313 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,740 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 276 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.