Hepatocyte transplantation: State of the art and strategies for overcoming existing hurdles

Lee, Sung W.; Wang, Xia; Chowdhury, Namita Roy; Roy‐Chowdhury, Jayanta

doi:10.1016/s1665-2681(19)32108-8

Cited by 60 publications

(41 citation statements)

References 43 publications

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“…The chronic shortage of donor livers suitable for orthotopic transplantation has generated interest in alternative therapies, including hepatocyte transplantation, especially regarding the treatment of life-threatening inherited metabolic disorders of the liver [1][2][3][4]. Clinical trials have already shown the feasibility and safety of transplanting genetically modified autologous and allogenic hepatocytes [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

et al. 2007

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The feasibility of in vitro mature mouse hepatocyte labeling with a novel iron oxide particle was assessed and the ability of 1.5-T magnetic resonance imaging (MRI) to track labeled mouse hepatocytes in syngenic recipient livers following intraportal cell transplantation was tested. Mouse hepatocytes were incubated with anionic iron oxide nanoparticles at various iron concentrations. Cell viability was assessed and iron oxide particle uptake quantified. Labeled hepatocytes were intraportally injected into 20 mice, while unlabeled hepatocytes were injected into two mice. Liver T2 values, spleen-to-muscle relative signal intensity (RI( spleen/muscle )), and liver-to-muscle relative signal intensity (RI( liver/muscle )) on gradient-echo T2-weighted imaging after injection of either labeled or unlabeled hepatocytes were compared with an ANOVA test followed by Fisher's a posteriori PLSD test. Livers, spleens and lungs were collected for histological analysis. Iron oxide particle uptake was saturable with a maximum iron content of 20 pg per cell and without viability alteration after 3 days of culture. Following labeled-cell transplantation, recipient livers showed well-defined nodular foci of low signal intensity on MRI--consistent with clusters of labeled hepatocytes on pathological analysis--combined with a significant decrease in both liver T2 values and liver-to-muscle RI( liver/muscle ) (P = 0.01) with minimal T2 values demonstrated 8 days after transplantation. Conventional MRI can demonstrate the presence of transplanted iron-labeled mature hepatocytes in mouse liver.

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Section: Introductionmentioning

confidence: 99%

In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

et al. 2007

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“…Patient survival is now greater than 90% at 1 year and nearing 80% at 5 years [6]. However, liver transplantation is not without problems, as the operation is still a formidable and costly procedure with significant morbidity and mortality [7]. It requires lifelong immunosuppression which in itself carries risks such as infection and malignancy.…”

Section: Liver Transplantation and The Need For Alternative Therapiesmentioning

confidence: 99%

“…The specialised extracellular matrix and portal blood supply make the liver the optimum site for transplanted hepatocytes to engraft and survive and so the liver itself is thought to be the most desirable site for transplantation [20]. This can be achieved by infusing hepatocytes directly into the portal vein or, using the spleen as a conduit, by injecting into the splenic pulp [7]. Intraportal infusion is a relatively straightforward technique, and the majority of the animal studies as well as procedures performed in humans, with one or two exceptions, have made use of this technique.…”

Section: Hepatocyte Transplantationmentioning

confidence: 99%

Hepatocyte cell therapy in liver disease

Bartlett

Newsome

2015

Expert Review of Gastroenterology & Hepatology

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Liver disease is a leading cause of morbidity and mortality. Liver transplantation remains the only proven treatment for end-stage liver failure but is limited by the availability of donor organs. Hepatocyte cell therapy, either with bioartificial liver devices or hepatocyte transplantation, may help address this by delaying or preventing liver transplantation. Early clinical studies have shown promising results, however in most cases, the benefit has been short lived and so further research into these therapies is required. Alternative sources of hepatocytes, including stem cell-derived hepatocytes, are being investigated as the isolation of primary human hepatocytes is limited by the same shortage of donor organs. This review summarises the current clinical experience of hepatocyte cell therapy together with an overview of possible alternative sources of hepatocytes. Current and future areas for research that might lead towards the realisation of the full potential of hepatocyte cell therapy are discussed.

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“…Correction of a genetic defect affecting a specific metabolic function of the liver may be possible through replacement of 1-5% of the diseased host liver parenchyma by transplanted healthy donor hepatocytes [60,61]. This has been shown for example in patients suffering from glycogen storage disease type Ia [62] or CriglerNajjar syndrome type I [63].…”

Section: How Much Do We Need?mentioning

confidence: 99%

The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver

Christ

Dollinger

2011

Current Opinion in Organ Transplantation

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Their versatile biological features render mesenchymal stem cells an alternate cell resource for the treatment of liver diseases. It is important to know the mechanisms of integration of transplanted cells into the recipient tissue and to understand the communication between donor cells and the host tissue on the molecular level in order to support efficacy of cell transplantation and thus optimize the therapeutical outcome.

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Hepatocyte transplantation: State of the art and strategies for overcoming existing hurdles

Cited by 60 publications

References 43 publications

In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

Hepatocyte cell therapy in liver disease

The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver

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