Hepatocyte Transplantation for the Treatment of Human Disease

Strom, Stephen C.; Chowdhury, Jayanta Roy; Fox, Ira J.

doi:10.1055/s-2007-1007096

Cited by 355 publications

(225 citation statements)

References 55 publications

(3 reference statements)

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“…The common feature in these diseases is loss or defective hepatocyte function and the only curative therapy is orthotopic liver transplant. However, since there is a severe shortage of suitable donor organs, transplantation of human fetal and adult hepatocytes is being evaluated [3][4][5][6]. However, hepatocyte transplantation is limited by the severe shortage of suitable liver resections for cell isolation, the large number of hepatocytes required for transplantation and difficulties associated with hepatocyte culture and cryopreservation [7].…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

Vaghjiani

Vaithilingam

Saraswati

et al. 2014

Stem Cells and Development

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Placenta derived human amniotic epithelial cells (hAEC) are an attractive source of stem cells for the generation of hepatocyte-like cells (HLC) for therapeutic applications to treat liver diseases. During hAEC differentiation into HLC, they become increasingly immunogenic, which may result in immune cell-mediated rejection upon transplantation into allogeneic recipients. Placing cells within devices such as alginate microcapsules can prevent immune cell-mediated rejection. The aim of this study was to investigate the characteristics of HLC generated from hAEC and to examine the effects of encapsulation on HLC viability, gene expression, and function. hAEC were differentiated for 4 weeks and evaluated for hepatocyte-specific gene expression and function. Differentiated cells were encapsulated in barium alginate microcapsules and cultured for 7 days and the effect of encapsulation on cell viability, function, and hepatocyte related gene expression was determined. Differentiated cells performed key functions of hepatocytes including urea synthesis, drug-metabolizing cytochrome P450 (CYP)3A4 activity, indocyanine green (ICG) uptake, low-density lipoprotein (LDL) uptake, and exhibited glutathione antioxidant capacity. A number of hepatocyte-related genes involved in fat, cholesterol, bile acid synthesis, and xenobiotic metabolism were also expressed showing that the hAEC had differentiated into HLC. Upon encapsulation, the HLC remained viable for at least 7 days in culture, continued to express genes involved in fat, cholesterol, bile acid, and xenobiotic metabolism and had glutathione antioxidant capacity. CYP3A4 activity and urea synthesis by the encapsulated HLC were higher than that of monolayer HLC cultures. Functional HLC can be derived from hAEC, and HLC can be encapsulated within alginate microcapsules without losing viability or function in vitro.

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Section: Introductionmentioning

confidence: 99%

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

Vaghjiani

Vaithilingam

Saraswati

et al. 2014

Stem Cells and Development

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“…However this area faces several challenges including the absence of a suitable cell source. [104][105][106] Use of a hepatic progenitor cell population is an attractive alternative because these cells possess not only a higher plasticity and survival capability but also a renewal ability. The positive impact of FGFs on hepatic progenitor pool expansion might find application in cell therapies, hepatic tissue engineering, and artificial liver devices.…”

Section: The Role Of Hepatocytes and Oval Cells In Liver Regenerationmentioning

confidence: 99%

Pluripotent plasticity of stem cells and liver repopulation

Gennero

Roos

Sperber

et al. 2010

Cell Biochemistry & Function

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Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver.

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“…2,3 It is reported that primary cultured hepatocytes are transplanted into patients with liver failure. 4 Cultured hepatocytes are prone to apoptosis and damage. 5 Moreover, they do not proliferate.…”

Section: Introductionmentioning

confidence: 99%

Dual Gene Expression in Embryoid Bodies Derived from Human Induced Pluripotent Stem Cells Using Episomal Vectors

Tomizawa

Shinozaki²,

Motoyoshi³

et al. 2014

Tissue Engineering Part A

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Transcription factors are essential for the differentiation of human induced pluripotent stem cells (iPS) into specialized cell types. Embryoid body (EB) formation promotes the differentiation of iPS cells. We sought to establish an efficient method of transfection and rotary culture to generate EBs that stably express two genes. The pMetLuc2-Reporter vector was transfected using FuGENE HD (FuGENE), Lipofectamine LTX (LTX), X-tremeGENE, or TransIT-2020 transfection reagents. The media was analyzed using a Metridia luciferase (MetLuc) assay. Transfections were performed on cells adherent to plates/dishes (adherent method) or suspended in the media (suspension method). The 201B7 cells transfected with episomal vectors were selected using G418 (200 mg/mL) or hygromycin B (300 mg/mL). Rotary culture was performed at 2.5 or 9.9 rpm. Efficiency of EB formation was compared among plates and dishes. Cell density was compared at 1.6 · 10 3 , · 10 4 , and · 10 5 cells/ mL. The suspended method of transfection using the FuGENE HD reagent was the most efficient. The expression of pEBMulti/Met-Hyg was detected 11 days posttransfection. Double transformants were selected 6 days posttransfection with pEBNK/EGFP-Neo and pEBNK/Cherry-Hyg. Both EGFP and CherryPicker were expressed in all of the surviving cells. EBs were formed most efficiently from cells cultured at a density of 1.6 · 10 5 cells/mL in six-well plates or 6 cm dishes. The selected cells formed EBs. FuGENE-mediated transfection of plasmids using the suspension method was effective in transforming iPS cells. Furthermore, the episomal vectors enabled us to perform a stable double transfection of EB-forming iPS cells.

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Hepatocyte Transplantation for the Treatment of Human Disease

Cited by 355 publications

References 55 publications

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

Pluripotent plasticity of stem cells and liver repopulation

Dual Gene Expression in Embryoid Bodies Derived from Human Induced Pluripotent Stem Cells Using Episomal Vectors

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