ArticleStem cell research & therapy2017
Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency.
Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Effects of argon plasma treatment on the osteoconductivity of bone grafting materials.Clinical oral investigations · 2020Trial
- Targeted Hepatic Delivery of Bioactive Molecules via Nanovesicles: Recent Developments and Emerging Directions.Journal of personalized medicine · 2025Review
- The therapeutic landscape of citrin deficiency.Journal of inherited metabolic disease · 2024Review
- SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy.International journal of molecular sciences · 2024Article
- Role of Exosomal Modulation of Macrophages in Liver Fibrosis.Journal of clinical and translational hepatology · 2024Review
- Sensor extended imaging workflow for creating fit for purpose models in basic and applied cell biology.Communications biology · 2024Review
- Article
- Organ Repair and Regeneration DuringTransplant international : official journal of the European Society for Organ Transplantation · 2023Review
- The Effects of Programmed Cell Death of Mesenchymal Stem Cells on the Development of Liver Fibrosis.Stem cells international · 2023Review
- Hyperammonemia in Inherited Metabolic Diseases.Cellular and molecular neurobiology · 2022Review
- Approaches to incorporate extracellular vesicles into exposure science, toxicology, and public health research.Journal of exposure science & environmental epidemiology · 2022Review
- Clinical, laboratory data and outcomes of 17 Iranian citrullinemia type 1 patients: Identification of five novelJIMD reports · 2022Article
- Identification of Novel Mutations in Chinese Infants With Citrullinemia.Frontiers in genetics · 2022Article
- Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia.Transplant international : official journal of the European Society for Organ Transplantation · 2021Article
- Understanding extracellular vesicle and nanoparticle heterogeneity: Novel methods and considerations.Proteomics · 2021Review
- Cytosolic Delivery of Argininosuccinate Synthetase Using a Cell-Permeant Miniature Protein.ACS central science · 2021Article
- Protective effect of resveratrol on citrullinemia type I-induced brain oxidative damage in male rats.Metabolic brain disease · 2021Article
- Human Liver Stem Cells: A Liver-Derived Mesenchymal Stromal Cell-Like Population With Pro-regenerative Properties.Frontiers in cell and developmental biology · 2021Review
- Extracellular Vesicles in the Development of the Non-Alcoholic Fatty Liver Disease: An Update.Biomolecules · 2020Review
- Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell-derived tumor growth in vitro and in vivo.International journal of cancer · 2020Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundArgininosuccinate 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.
methodsHLSCs 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.
resultsTreating 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.
conclusionsCollectively, 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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