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Exosomes from mesenchymal stem cells induce the conversion of hepatocytes into progenitor oval cells

Overview of attention for article published in Stem Cell Research & Therapy, May 2017
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Title
Exosomes from mesenchymal stem cells induce the conversion of hepatocytes into progenitor oval cells
Published in
Stem Cell Research & Therapy, May 2017
DOI 10.1186/s13287-017-0560-z
Pubmed ID
Authors

Hao-Hsiang Wu, Oscar K. Lee

Abstract

We previously reported that mesenchymal stem cells (MSCs) possess therapeutic effects in a murine model of carbon tetrachloride-induced acute liver failure. In the study, we observed that the majority of repopulated hepatocytes were of recipient origin and were adjacent to transplanted MSCs; only a low percentage of repopulated hepatocytes were from transplanted MSCs. The findings indicate that MSCs guided the formation of new hepatocytes. Exosomes are important messengers for paracrine signaling delivery. The aim of this study is to investigate the paracrine effects, in particular, the effects of exosomes from MSCs, on hepatocytes. Mature hepatocytes were isolated from murine liver by a two-step perfusion method with collagenase digestion. MSCs were obtained from murine bone marrow, and conditioned medium (CM) from MSC culture was then collected. Time-lapse imaging was used for observation of cell morphological change induced by CM on hepatocytes. In addition, expression of markers for hepatic progenitors including oval cells, intrahepatic stem cells, and hepatoblasts were analyzed. Treatment with the CM promoted the formation of small oval cells from hepatocytes; time-lapse imaging demonstrated the change from epithelial to oval cell morphology at the single hepatocyte level. Additionally, expression of EpCAM and OC2, markers of hepatic oval cells, was upregulated. Also, the number of EpCAM(high) cells was increased after CM treatment. The EpCAM(high) small oval cells possessed colony-formation ability; they also expressed cytokeratin 18 and were able to store glycogen upon induction of hepatic differentiation. Furthermore, exosomes from MSC-CM could induce the conversion of mature hepatocytes to EpCAM(high) small oval cells. In summary, paracrine signaling through exosomes from MSCs induce the conversion of hepatocytes into hepatic oval cells, a mechanism of action which has not been reported regarding the therapeutic potentials of MSCs in liver regeneration. Exosomes from MSCs may therefore be used to treat liver diseases. Further studies are required for proof of concept of this approach.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 55 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 18%
Student > Master 9 16%
Student > Doctoral Student 7 13%
Student > Postgraduate 5 9%
Student > Bachelor 4 7%
Other 9 16%
Unknown 11 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 25%
Medicine and Dentistry 11 20%
Pharmacology, Toxicology and Pharmaceutical Science 4 7%
Immunology and Microbiology 3 5%
Agricultural and Biological Sciences 2 4%
Other 6 11%
Unknown 15 27%
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 18 July 2017.
All research outputs
#20,436,330
of 22,990,068 outputs
Outputs from Stem Cell Research & Therapy
#2,058
of 2,429 outputs
Outputs of similar age
#272,943
of 313,685 outputs
Outputs of similar age from Stem Cell Research & Therapy
#65
of 69 outputs
Altmetric has tracked 22,990,068 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 2,429 research outputs from this source. They typically receive a little more attention than average, with 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 313,685 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 69 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.