Hepatocyte cell therapy in liver disease

Bartlett, David; Newsome, Philip N.

doi:10.1586/17474124.2015.1073106

Cited by 21 publications

(13 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell-based therapeutics attempt to harness this power to treat problems that fall beyond the scope of traditional pharmacology. These cells can be administered directly into the patient's body in a procedure known as cell transplantation, but may also be used to populate extracorporeal assist devices (4). Cell therapy can be categorized according to the type of cell used and its duration within the body (Table 1).…”

Section: Cell Therapymentioning

confidence: 99%

“…The role that cell therapy may play in the treatment of CLD is two-fold. By stimulating endogenous regeneration and inhibiting fibrosis, cell therapy may curb disease progression, thus ideally eliminating the need for liver transplantation (4). In the cases where liver transplantation cannot be avoided, cell therapy may serve as a means for liver function support and act as a bridge to surgery, in theory decreasing waitlist mortality rates.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cell therapy in chronic liver disease

Nicolas

Wang

Nyberg

2016

Current Opinion in Gastroenterology

View full text Add to dashboard Cite

Purpose of review To date, the only curative treatment for end-stage liver disease is liver transplantation, which is limited by the shortage of available organs. Cell therapy, in the form of cell transplantation or cell-based extracorporeal support devices, may in the future offer an alternative to transplantation, or at least provide liver function support as a bridging therapy until surgery may be performed. The purpose of this review is to highlight the most recent advances made in the field of cell therapy and regenerative medicine for the treatment of chronic liver disease (CLD). Recent findings After hepatocyte transplantation, long-term engraftment in the liver and spleen may be achieved, which can be stimulated through preconditioning, multiple infusions, and inflammatory response blockade. Mesenchymal stem cells are promising candidates for cell transplantation, as they have been shown to reduce liver fibrosis and support endogenous regeneration. Adipose tissue-derived stem cells are also being tested in this setting, due to their ready availability. Bioartificial liver (BAL) devices are being built that allow for effective preservation of hepatocytes, and one such device has recently demonstrated survival benefit in a porcine model of liver failure. Summary Cell transplantation of primary hepatocytes or stem cell-derived hepatocyte-like cells (HLCs) for the treatment of CLD holds promise. BAL systems may in the future be able to bridge acute-on-chronic liver failure patients to liver transplantation.

show abstract

Section: Cell Therapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell therapy in chronic liver disease

Nicolas

Wang

Nyberg

2016

Current Opinion in Gastroenterology

View full text Add to dashboard Cite

show abstract

“…Orthotopic liver transplantation (OLT) is the only effective treatment for end-stage liver diseases, but there is currently a severe shortage of liver grafts available for transplantation [ 1 ]. Functional hepatocytes not only have therapeutic value for regenerative medicine and pharmacology research but also may be an attractive alternative to OLT [ 2 , 3 ]. Human primary hepatocytes are a ideal cellular resources for achieving these aims.…”

Section: Introductionmentioning

confidence: 99%

Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails

Feng

Qiu

et al. 2018

Stem Cell Res Ther

View full text Add to dashboard Cite

BackgroundThe advent of human-induced pluripotent stem cells holds great promise for producing ample individualized hepatocytes. Although previous efforts have succeeded in generating hepatocytes from human pluripotent stem cells in vitro by viral-based expression of transcription factors and/or addition of growth factors during the differentiation process, the safety issue of viral transduction and high cost of cytokines would hinder the downstream applications. Recently, the use of small molecules has emerged as a powerful tool to induce cell fate transition for their superior stability, safety, cell permeability, and cost-effectiveness.MethodsIn the present study, we established a novel efficient hepatocyte differentiation strategy of human pluripotent stem cells with pure small-molecule cocktails. This method induced hepatocyte differentiation in a stepwise manner, including definitive endoderm differentiation, hepatic specification, and hepatocyte maturation within only 13 days.ResultsThe differentiated hepatic-like cells were morphologically similar to hepatocytes derived from growth factor-based methods and primary hepatocytes. These cells not only expressed specific hepatic markers at the transcriptional and protein levels, but also possessed main liver functions such as albumin production, glycogen storage, cytochrome P450 activity, and indocyanine green uptake and release.ConclusionsHighly efficient and expedited hepatic differentiation from human pluripotent stem cells could be achieved by our present novel, pure, small-molecule cocktails strategy, which provides a cost-effective platform for in vitro studies of the molecular mechanisms of human liver development and holds significant potential for future clinical applications.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0794-4) contains supplementary material, which is available to authorized users.

show abstract

“…Cell replacement therapies using hepatocytes generated in vitro may be useful in treating fatal liver disease [ 1 , 2 ]. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are promising resources for cell therapy because they can expand continuously in an undifferentiated state and can produce any type of tissue given appropriate conditions [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Enrichment of Pluripotent Stem Cell-Derived Hepatocyte-Like Cells by Ammonia Treatment

et al. 2016

View full text Add to dashboard Cite

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are potential resources for the regeneration of defective organs, including the liver. However, some obstacles must be overcome before this becomes reality. Undifferentiated cells that remain following differentiation have teratoma-forming potential. Additionally, practical applications require a large quantity of differentiated cells, so the differentiation process must be economical. Here we describe a DNA microarray-based global analysis of the gene expression profiles of differentiating human pluripotent stem cells. We identified differences and commonalities among six human pluripotent stem cell lines: the hESCs KhES1, KhES2, KhES3, and H1, and the iPSCs 201B7 and 243G1. Embryoid bodies (EBs) formed without requiring supplementation with inducing factors. EBs also expressed some liver-specific metabolic genes including the ammonia-metabolizing enzymes glutamine synthetase and carbamoyl-phosphate synthase 1. Real-time PCR analysis revealed hepatocyte-like differentiation of EBs treated with ammonia in Lanford medium. Analysis of DNA microarray data suggested that hepatocyte-like cells were the most abundant population in ammonia-treated cells. Furthermore, expression levels of undifferentiated pluripotent stem cell markers were drastically reduced, suggesting a reduced teratoma-forming capacity. These results indicate that treatment of EBs with ammonia in Lanford medium may be an effective inducer of hepatic differentiation in absence of expensive inducing factors.

show abstract

Hepatocyte cell therapy in liver disease

Cited by 21 publications

References 116 publications

Cell therapy in chronic liver disease

Cell therapy in chronic liver disease

Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails

Enrichment of Pluripotent Stem Cell-Derived Hepatocyte-Like Cells by Ammonia Treatment

Contact Info

Product

Resources

About