ArticleHepatology (Baltimore, Md.)2014
Repopulation of the fibrotic/cirrhotic rat liver by transplanted hepatic stem/progenitor cells and mature hepatocytes.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed.
- Sweet and sticky: increased cell adhesion through click-mediated functionalization of regenerative liver progenitor cells.Communications biology · 2025Article
- Functional mouse hepatocytes derived from interspecies chimeric livers effectively mitigate chronic liver fibrosis.Stem cell reports · 2024Article
- A High-Fat and High-Fructose Diet Exacerbates Liver Dysfunction by Regulating Sirtuins in a Murine Model.Life (Basel, Switzerland) · 2024Article
- Article
- Antagonizing Activin A/p15Cells · 2024Article
- Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues.Cells · 2023Review
- Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis.World journal of gastrointestinal oncology · 2022Article
- Single cell Raman spectroscopy to identify different stages of proliferating human hepatocytes for cell therapy.Stem cell research & therapy · 2021Article
- Co-culture with mouse embryonic fibroblasts improves maintenance of metabolic function of human small hepatocyte progenitor cells.Current research in toxicology · 2020Article
- A novel stem cell therapy for hepatitis B virus-related acute-on-chronic liver failure.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Therapeutic targets for liver regeneration after acute severe injury: a preclinical overview.Expert opinion on therapeutic targets · 2020Review
- Synergistic modulation of signaling pathways to expand and maintain the bipotency of human hepatoblasts.Stem cell research & therapy · 2019Article
- A murine model demonstrating reversal of structural and functional correlates of cirrhosis with progenitor cell transplantation.Scientific reports · 2019Article
- Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver.Experimental and therapeutic medicine · 2019Article
- Biliary Obstruction Promotes Multilineage Differentiation of Hepatic Stem Cells.Hepatology communications · 2019Article
- The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation.Stem cells international · 2019Article
- InGene expression · 2018Article
- Liver cell therapy: is this the end of the beginning?Cellular and molecular life sciences : CMLS · 2018Review
- Liver epithelioid progenitor cells derived from fetal Luxi bovine alleviate liver fibrosis.Cytotechnology · 2018Article
- Liver function tests in identifying patients with liver disease.Clinical and experimental gastroenterology · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
unlabelledConsiderable progress has been made in developing antifibrotic agents and other strategies to treat liver fibrosis; however, significant long-term restoration of functional liver mass has not yet been achieved. Therefore, we investigated whether transplanted hepatic stem/progenitor cells can effectively repopulate the liver with advanced fibrosis/cirrhosis. Stem/progenitor cells derived from fetal livers or mature hepatocytes from DPPIV(+) F344 rats were transplanted into DPPIV(-) rats with thioacetamide (TAA)-induced fibrosis/cirrhosis; rats were sacrificed 1, 2, or 4 months later. Liver tissues were analyzed by histochemistry, hydroxyproline determination, reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. After chronic TAA administration, DPPIV(-) F344 rats exhibited progressive fibrosis, cirrhosis, and severe hepatocyte damage. Besides stellate cell activation, increased numbers of stem/progenitor cells (Dlk-1(+), AFP(+), CD133(+), Sox-9(+), FoxJ1(+)) were observed. In conjunction with partial hepatectomy (PH), transplanted stem/progenitor cells engrafted, proliferated competitively compared to host hepatocytes, differentiated into hepatocytic and biliary epithelial cells, and generated new liver mass with extensive long-term liver repopulation (40.8 ± 10.3%). Remarkably, more than 20% liver repopulation was achieved in the absence of PH, associated with reduced fibrogenic activity (e.g., expression of alpha smooth muscle actin, platelet-derived growth factor receptor β, desmin, vimentin, tissue inhibitor of metalloproteinase-1) and fibrosis (reduced collagen). Furthermore, hepatocytes can also replace liver mass with advanced fibrosis/cirrhosis, but to a lesser extent than fetal liver stem/progenitor cells.
conclusionThis study is a proof of principle demonstration that transplanted epithelial stem/progenitor cells can restore injured parenchyma in a liver environment with advanced fibrosis/cirrhosis and exhibit antifibrotic effects.
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