Orthotopic liver transplantation remains the only curative treatment for liver disease. However, the number of patients who die while on the waiting list (15%) has increased in recent years as a result of severe organ shortages; furthermore the incidence of liver disease is increasing worldwide. Clinical trials involving hepatocyte transplantation have provided encouraging results. However, transplanted cell function appears to often decline after several months, necessitating liver transplantation. The precise aetiology of the loss of cell function is not clear, but poor engraftment and immune-mediated loss appear to be important factors. Also, primary human hepatocytes (PHH) are not readily available, de-differentiate, and die rapidly in culture. Hepatocytes are available from other sources, such as tumour-derived human hepatocyte cell lines and immortalised human hepatocyte cell lines or porcine hepatocytes. However, all these cells suffer from various limitations such as reduced or differences in functions or risk of zoonotic infections. Due to their significant potential, one possible inexhaustible source of hepatocytes is through the directed differentiation of human induced pluripotent stem cells (hiPSCs). This review will discuss the potential applications and existing limitations of hiPSC-derived hepatocytes in regenerative medicine, drug screening, in vitro disease modelling and bioartificial livers.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jhep.2016.02.025 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A NOTCH3 pathogenic variant influences osteogenesis and can be targeted by antisense oligonucleotides in induced pluripotent stem cells.
PLoS One
January 2025
Ionis Pharmaceuticals, Inc., Carlsbad, CA, United States of America.
Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Pennsylvania, Philadelphia, PA, USA.
Background: Tau is a neuronal microtubule associated protein whose interactions with microtubules are regulated by phosphorylation. Tau has numerous putative phosphorylation sites, but it is unclear which combinations of Tau phosphorylation co-occur in the normal state and precisely how they impact Tau function. Adding further complexity, there are six major Tau isoforms arising from alternative splicing.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
German Center for Neurodegenerative Diseases (DZNE), Munich, Bavaria, Germany.
Background: Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-GRN). Multiple therapeutic strategies are in clinical development to restore PGRN levels in the CNS, including gene therapy. However, a limitation of current gene therapy approaches aimed to alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: The Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) is a public-private partnership linking NIH, the FDA, pharmaceutical companies, and nonprofit organizations in an interactive, collaborative program utilizing transcriptomics, genomics, metagenomics, proteomics, and metabolomics to provide data for computational analysis, that, in turn, enables promising targets to be ranked by a combination of omic scores and druggability. This ranking informs the selection of targets for validation.
Method: Human postmortem samples were obtained from Mount Sinai, ROSMAP (Religious Orders Study and Rush Memory and Aging Project), Mayo Clinic (Florida), and Columbia University.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Background: We aim to investigate efficacies of Ras homolog (Rho)-associated kinases (ROCK) inhibitors on Alzheimer's disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)-differentiated human neurons and the P301S tau transgenic mouse model (PS19).
Method: Quantitative liquid chromatography-mass spectrometry (LC-MS/MS) and targeted ELISA were implemented to investigate the effect of treatment with fasudil or its derivatives on the human neurons and brains from PS19 mice. We explored the efficacy of these ROCK inhibitors in reducing tau phosphorylation, and the brain proteomic profiles after their administration in mice.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!