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Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency

Overview of attention for article published in Stem Cell Research & Therapy, July 2017
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  • Good Attention Score compared to outputs of the same age (66th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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2 patents

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Title
Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency
Published in
Stem Cell Research & Therapy, July 2017
DOI 10.1186/s13287-017-0628-9
Pubmed ID
Authors

Maria Beatriz Herrera Sanchez, Sara Previdi, Stefania Bruno, Valentina Fonsato, Maria Chiara Deregibus, Sharad Kholia, Sara Petrillo, Emanuela Tolosano, Rossana Critelli, Marco Spada, Renato Romagnoli, Mauro Salizzoni, Ciro Tetta, Giovanni Camussi

Abstract

Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for this disease is currently restricted to liver transplantation; however, due to limited organ availability, substitute therapies are required. Recently, extracellular vesicles (EVs) have been reported to act as intercellular transporters carrying genetic information responsible for cell reprogramming. In previous studies, we isolated a population of stem cell-like cells known as human liver stem cells (HLSCs) from healthy liver tissue. Moreover, EVs derived from HLSCs were reported to exhibit regenerative effects on the liver parenchyma in models of acute liver injury. The aim of this study was to evaluate whether EVs derived from normal HLSCs restored ASS1 enzymatic activity and urea production in hepatocytes differentiated from HLSCs derived from a patient with type I citrullinemia. HLSCs were isolated from the liver of a patient with type I citrullinemia (ASS1-HLSCs) and characterized by fluorescence-activated cell sorting (FACS), immunofluorescence, and DNA sequencing analysis. Furthermore, their differentiation capabilities in vitro were also assessed. Hepatocytes differentiated from ASS1-HLSCs were evaluated by the production of urea and ASS enzymatic activity. EVs derived from normal HLSCs were purified by differential ultracentrifugation followed by floating density gradient. The EV content was analyzed to identify the presence of ASS1 protein, mRNA, and ASS1 gene. In order to obtain ASS1-depleted EVs, a knockdown of the ASS1 gene in HLSCs was performed followed by EV isolation from these cells. Treating ASS1-HLSCs with EVs from HLSCs restored both ASS1 activity and urea production mainly through the transfer of ASS1 enzyme and mRNA. In fact, EVs from ASS1-knockdown HLSCs contained low amounts of ASS1 mRNA and protein, and were unable to restore urea production in hepatocytes differentiated from ASS1-HLSCs. Collectively, these results suggest that EVs derived from normal HLSCs may compensate the loss of ASS1 enzyme activity in hepatocytes differentiated from ASS1-HLSCs.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 17%
Researcher 7 15%
Student > Master 6 13%
Student > Bachelor 3 6%
Other 3 6%
Other 6 13%
Unknown 14 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 38%
Medicine and Dentistry 8 17%
Agricultural and Biological Sciences 2 4%
Engineering 2 4%
Chemistry 1 2%
Other 1 2%
Unknown 15 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 17 December 2020.
All research outputs
#6,484,366
of 22,994,508 outputs
Outputs from Stem Cell Research & Therapy
#627
of 2,429 outputs
Outputs of similar age
#104,122
of 317,332 outputs
Outputs of similar age from Stem Cell Research & Therapy
#9
of 51 outputs
Altmetric has tracked 22,994,508 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
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 has gotten more attention than average, scoring higher than 73% of its peers.
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 317,332 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 51 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.