ArticleJCI insight2019
Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Systematic review of exosomes derived from various stem cell sources: function and therapeutic potential in disease modulation.Molecular biology reports · 2025Pooled it
- Secretome of Stem Cells: Roles of Extracellular Vesicles in Diseases, Stemness, Differentiation, and Reprogramming.Tissue engineering and regenerative medicine · 2022Pooled it
- Profiling of extracellular vesicles from primary hepatocytes, organoids, and mash patients identifies cell injury-specific signatures.Scientific reports · 2026Article
- Review
- Extracellular vesicles derived from induced pluripotent stem cells mediate anti-inflammatory effects in primary human macrophages.Scientific reports · 2026Article
- The harmonies played by miR-302/367 cluster in pluripotency, reprogramming, and rejuvenation.Stem cells translational medicine · 2026Review
- Recent Updates on Molecular and Physical Therapies for Organ Fibrosis.Molecules (Basel, Switzerland) · 2025Review
- Extracellular vesicles in metabolic dysfunction-associated steatotic liver disease: From intercellular signaling to clinical translation.World journal of hepatology · 2025Review
- Human induced pluripotent stem cell derived nanovesicles for cardiomyocyte protection and proliferation.Bioactive materials · 2025Article
- Extracellular Vesicles and Micro-RNAs in Liver Disease.Seminars in liver disease · 2025Review
- MFGE-8, a Corona Protein on Extracellular Vesicles, Mediates Self-Renewal and Survival of Human Pluripotent Stem Cells.Journal of extracellular vesicles · 2025Article
- Extracellular vesicles derived from "serum and glucose" deprived HUCMSCs promoted skin wound healing through enhanced angiogenesis.Molecular and cellular biochemistry · 2025Article
- Sinusoidal communication in chronic liver disease.Clinical and molecular hepatology · 2025Review
- Extracellular vesicles: emerging therapeutic agents for liver fibrosis.Extracellular vesicles and circulating nucleic acids · 2025Review
- The Role of Extracellular Vesicles in Liver Fibrosis: Friends or Foes?Biomedicines · 2024Review
- Extracellular Vesicles in Viral Liver Diseases.Viruses · 2024Review
- Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis.Journal of nanobiotechnology · 2024Article
- Stem cell-based therapy for fibrotic diseases: mechanisms and pathways.Stem cell research & therapy · 2024Review
- Human umbilical cord-derived mesenchymal stem cells attenuate hepatic stellate cells activation and liver fibrosis.Molecular biology reports · 2024Article
- Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis.Clinical nutrition ESPEN · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Progression of fibrosis and the development of cirrhosis are responsible for the liver related morbidity and mortality associated with chronic liver diseases. There is currently a great unmet need for effective anti-fibrotic strategies. Stem cells play a central role in wound healing responses to restore liver homeostasis following injury. Here we tested the hypothesis that extracellular vesicles (EVs) isolated from induced pluripotent stem cells (iPSC) modulate hepatic stellate cell (HSCs) activation and may have anti-fibrotic effects. Human iPSCs were generated by reprogramming primary skin fibroblasts. EVs were isolated by differential centrifugation, quantified by flow cytometry (FACS) and characterized by dynamic light scattering (DLS) and electron microscopy (TEM). Primary human HSCs were activated with TGFβ (10 ng/mL) and exposed to iPSC-EVs. Efficacy of iPSC-EVs was tested on HSC in vitro and in two murine models of liver injury (CCl4 and bile duct ligation). Characterization of iPSC-derived EVs by flow cytometry identified a large population of EVs released by iPSC, primarily with a diameter of 300 nm and that could be visualized by TEM as round, cup-shaped objects. Fluorescent tracing assays detected iPSC-EVs in HSC cytosol after a short incubation and EV uptake by HSCs resulted in both decrease of pro-fibrogenic markers αSMA, CollagenIα1, Fibronectin and TIMP-1 and HSC pro-fibrogenic responses such as chemotaxis and proliferation. Genomics analyses of iPSC-EV miRNA cargo revealed 22 highly expressed miRNAs, among which miR-92a-3p resulted the most abundant. Transcriptome analysis identified 60 genes down-modulated and 235 up-regulated in TGF-β-primed HSC in presence or absence of iPSC-EVs. Intravenous injection of iPSC-EVs in CCl4 and bile duct ligation-induced liver fibrosis resulted in anti-fibrotic effects at protein and gene levels. Results of this study identify iPSC-EVs as a novel anti-fibrotic approach that may reduce or reverse liver fibrosis in patients with chronic liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.