ArticleSurgery2018
Hepatocyte spheroids as an alternative to single cells for transplantation after ex vivo gene therapy in mice and pig models.
Article in Surgery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Three-Dimensional Culture of Primary Hepatocytes in a Single-Cell Layer on Poly(vinyl alcohol) Nanofibrous Membrane.International journal of molecular sciences · 2026Article
- In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions.Nature communications · 2022Article
- Preservation of heparin-binding EGF-like growth factor activity on heparin-modified poly(RSC advances · 2021Article
- Production of Multiple Cell-Laden Microtissue Spheroids with a Biomimetic Hepatic-Lobule-Like Structure.Advanced materials (Deerfield Beach, Fla.) · 2021Article
- [Rapid screening of single guide RNA targeting pig genome and the harvesting of monoclonal cells by microarray seal].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2021Article
- Cyclotron Production of PET Radiometals in Liquid Targets: Aspects and Prospects.Current radiopharmaceuticals · 2021Review
- Current Perspectives onInternational journal of molecular sciences · 2020Review
- The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.Expert opinion on orphan drugs · 2020Article
- The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats.International journal of molecular sciences · 2019Article
- Hepatocyte Transplantation to the Liver via the Splenic Artery in a Juvenile Large Animal Model.Cell transplantation · 2019Article
- Investigation of Clinical Safety of Human iPS Cell-Derived Liver Organoid Transplantation to Infantile Patients in Porcine Model.Cell transplantationArticle
- The Efficacy of the Hepatocyte Spheroids for Hepatocyte Transplantation.Cell transplantationArticle
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAutologous hepatocyte transplantation after ex vivo gene therapy is an alternative to liver transplantation for metabolic liver disease. Here we evaluate ex vivo gene therapy followed by transplantation of single-cell or spheroid hepatocytes.
methodsPig and mouse hepatocytes were isolated, labeled with zirconium-89 and returned to the liver as single cells or spheroids. Biodistribution was evaluated through positron emission tomography-computed tomography. Fumarylacetoacetate hydrolase-deficient pig hepatocytes were isolated and transduced with a lentiviral vector containing the Fah gene. Animals received portal vein infusion of single-cell or spheroid autologous hepatocytes after ex vivo gene delivery. Portal pressures were measured and ultrasound was used to evaluate for thrombus. Differences in engraftment and expansion of ex vivo corrected single-cell or spheroid hepatocytes were followed through histologic analysis and animals' ability to thrive off 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione.
resultsPositron emission tomography-computed tomography imaging showed spheroid hepatocytes with increased heterogeneity in biodistribution as compared with single cells, which spread more uniformly throughout the liver. Animals receiving spheroids experienced higher mean changes in portal pressure than animals receiving single cells (P < .01). Additionally, two animals from the spheroid group developed portal vein thrombi that required systemic anticoagulation. Immunohistochemical analysis of spheroid- and single-cell-transplanted animals showed similar engraftment and expansion rates of fumarylacetoacetate hydrolase-positive hepatocytes in the liver, correlating with similar weight stabilization curves.
conclusionEx vivo gene correction of autologous hepatocytes in fumarylacetoacetate hydrolase-deficient pigs can be performed using hepatocyte spheroids or single-cell hepatocytes, with spheroids showing a more heterogeneous distribution within the liver and higher risks for portal vein thrombosis and increased portal pressures.
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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.