ArticleHepatology (Baltimore, Md.)2013
Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
130 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.
- Brain imaging genetics in ADHD and beyond - Mapping pathways from gene to disorder at different levels of complexity.Neuroscience and biobehavioral reviews · 2017Pooled it
- Diversity-in-a-dish: A practical framework for hiPSC model development.Stem cell reports · 2026Review
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Application potential of induced pluripotent stem cells in the research and treatment of autoimmune diseases (Review).Molecular medicine reports · 2025Review
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Next-Generation Regenerative Therapies for Alpha-1 Antitrypsin Deficiency: Molecular Pathogenesis to Clinical Translation.International journal of molecular sciences · 2025Review
- Functional Liver Cell-Based Platforms in Biomedical Research.Pharmacology research & perspectives · 2025Review
- A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- Therapeutic Potential of Extracellular Vesicles from Different Stem Cells in Chronic Wound Healing.Stem cell reviews and reports · 2023Review
- Engineering considerations of iPSC-based personalized medicine.Biomaterials research · 2023Review
- Expression of the Z Variant of α1-Antitrypsin Suppresses Hepatic Cholesterol Biosynthesis in Transgenic Zebrafish.International journal of molecular sciences · 2023Article
- Stem Cell-Based Therapeutic Approaches in Genetic Diseases.Advances in experimental medicine and biology · 2023Article
- Induced pluripotent stem cell-based therapies for organ fibrosis.Frontiers in bioengineering and biotechnology · 2023Review
- Role of in vitro two-dimensional (2D) and three-dimensional (3D) cell culture systems for ADME-Tox screening in drug discovery and development: a comprehensive review.ADMET & DMPK · 2023Review
- Consideration of Commercially Available Hepatocytes as Cell Sources for Liver-Microphysiological Systems by Comparing Liver Characteristics.Pharmaceutics · 2022Article
- From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation.Seminars in liver disease · 2022Article
- Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages.Toxicology in vitro : an international journal published in association with BIBRA · 2022Review
- Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells.Genes · 2022Review
- Wnt signaling in biliary development, proliferation, and fibrosis.Experimental biology and medicine (Maywood, N.J.) · 2022Review
70 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
10 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledPatient-specific induced pluripotent stem cells (iPSCs) represent a potential source for developing novel drug and cell therapies. Although increasing numbers of disease-specific iPSCs have been generated, there has been limited progress in iPSC-based drug screening/discovery for liver diseases, and the low gene-targeting efficiency in human iPSCs warrants further improvement. Using iPSC lines from patients with alpha-1 antitrypsin (AAT) deficiency, for which there is currently no drug or gene therapy available, we established a platform to discover new drug candidates and correct disease-causing mutation with a high efficiency. A high-throughput format screening assay, based on our hepatic differentiation protocol, was implemented to facilitate automated quantification of cellular AAT accumulation using a 96-well immunofluorescence reader. To expedite the eventual application of lead compounds to patients, we conducted drug screening utilizing our established library of clinical compounds (the Johns Hopkins Drug Library) with extensive safety profiles. Through a blind large-scale drug screening, five clinical drugs were identified to reduce AAT accumulation in diverse patient iPSC-derived hepatocyte-like cells. In addition, using the recently developed transcription activator-like effector nuclease technology, we achieved high gene-targeting efficiency in AAT-deficiency patient iPSCs with 25%-33% of the clones demonstrating simultaneous targeting at both diseased alleles. The hepatocyte-like cells derived from the gene-corrected iPSCs were functional without the mutant AAT accumulation. This highly efficient and cost-effective targeting technology will broadly benefit both basic and translational applications.
conclusionsOur results demonstrated the feasibility of effective large-scale drug screening using an iPSC-based disease model and highly robust gene targeting in human iPSCs, both of which are critical for translating the iPSC technology into novel therapies for untreatable diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.