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Human Amniotic Epithelial Cell Transplantation Induces Markers of Alternative Macrophage Activation and Reduces Established Hepatic Fibrosis

Overview of attention for article published in PLOS ONE, June 2012
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Title
Human Amniotic Epithelial Cell Transplantation Induces Markers of Alternative Macrophage Activation and Reduces Established Hepatic Fibrosis
Published in
PLOS ONE, June 2012
DOI 10.1371/journal.pone.0038631
Pubmed ID
Authors

Ursula Manuelpillai, Dinushka Lourensz, Vijesh Vaghjiani, Jorge Tchongue, Derek Lacey, Jing-Yang Tee, Padma Murthi, James Chan, Alexander Hodge, William Sievert

Abstract

Chronic hepatic inflammation from multiple etiologies leads to a fibrogenic response that can progress to cirrhosis and liver failure. Transplantation of human amniotic epithelial cells (hAEC) from term delivered placenta has been shown to decrease mild to moderate hepatic fibrosis in a murine model. To model advanced human liver disease and assess the efficacy of hAEC therapy, we transplanted hAEC in mice with advanced hepatic fibrosis. Immunocompetent C57BL/6 mice were administered carbon tetrachloride (CCl(4)) twice weekly resulting in bridging fibrosis by 12 weeks. hAEC (2 × 10(6)) were infused via the tail vein at week 8 or weeks 8 and 10 (single and double dose, respectively). Human cells were detected in mouse liver four weeks after transplantation showing hAEC engraftment. CCl(4) treated mice receiving single or double hAEC doses showed a significant but similar decrease in liver fibrosis area associated with decreased activation of collagen-producing hepatic stellate cells and decreased hepatic protein levels of the pro-fibrogenic cytokine, transforming growth factor-beta1. CCl(4) administration caused hepatic T cell infiltration that decreased significantly following hAEC transplantation. Hepatic macrophages play a crucial role in both fibrogenesis and fibrosis resolution. Mice exposed to CCl(4) demonstrated increased numbers of hepatic macrophages compared to normal mice; the number of macrophages decreased significantly in CCl(4) treated mice given hAEC. These mice had significantly lower hepatic protein levels of the chemokine monocyte chemoattractant protein-1 than mice given CCl(4) alone. Alternatively activated M2 macrophages are associated with fibrosis resolution. CCl(4) treated mice given hAEC showed increased expression of genes associated with M2 macrophages including YM-1, IL-10 and CD206. We provide novel data showing that hAEC transplantation induces a wound healing M2 macrophage phenotype associated with reduction of established hepatic fibrosis that justifies further investigation of this potential cell-based therapy for advanced hepatic fibrosis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 68 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 18 26%
Researcher 11 16%
Student > Doctoral Student 6 9%
Student > Bachelor 6 9%
Professor > Associate Professor 5 7%
Other 12 18%
Unknown 10 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 26%
Medicine and Dentistry 13 19%
Agricultural and Biological Sciences 12 18%
Immunology and Microbiology 4 6%
Engineering 4 6%
Other 2 3%
Unknown 15 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 December 2012.
All research outputs
#14,146,599
of 22,668,244 outputs
Outputs from PLOS ONE
#115,550
of 193,511 outputs
Outputs of similar age
#98,564
of 167,326 outputs
Outputs of similar age from PLOS ONE
#2,183
of 3,847 outputs
Altmetric has tracked 22,668,244 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,511 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 36th percentile – i.e., 36% 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 167,326 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,847 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.