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Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction.

Sharma R, Greenhough S, Medine CN, Hay DC - J. Biomed. Biotechnol. (2010)

Bottom Line: The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality.The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes.Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, 49 Little France Crescent, Edinburgh,Scotland EH16 4SB, UK.

ABSTRACT
The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

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Schematic diagram of the derivation of hepatic endoderm from human embryonic stem cells.
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fig1: Schematic diagram of the derivation of hepatic endoderm from human embryonic stem cells.

Mentions: Using developmental signalling physiology, it is possible to drive hESC differentiation to functional HE [47–60]. This can be achieved either by spontaneous differentiation through the formation of embryoid bodies (EBs), or by direct differentiation (Figure 1). Spontaneous differentiation of hESCs results in the formation of EBs consisting of a mixed cell population of all three germ layers [48]. These EBs have been shown to differentiate spontaneously into HE [47, 49, 50], but this occurs with limited efficiency. Recently, specific growth factors have been identified to direct hepatic differentiation following EB formation. However, differentiated cell populations still require purification following this process [51]. A number of studies have shown that faster, more efficient production of HE can be achieved through direct differentiation without the formation of EBs [52–57].


Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction.

Sharma R, Greenhough S, Medine CN, Hay DC - J. Biomed. Biotechnol. (2010)

Schematic diagram of the derivation of hepatic endoderm from human embryonic stem cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821762&req=5

fig1: Schematic diagram of the derivation of hepatic endoderm from human embryonic stem cells.
Mentions: Using developmental signalling physiology, it is possible to drive hESC differentiation to functional HE [47–60]. This can be achieved either by spontaneous differentiation through the formation of embryoid bodies (EBs), or by direct differentiation (Figure 1). Spontaneous differentiation of hESCs results in the formation of EBs consisting of a mixed cell population of all three germ layers [48]. These EBs have been shown to differentiate spontaneously into HE [47, 49, 50], but this occurs with limited efficiency. Recently, specific growth factors have been identified to direct hepatic differentiation following EB formation. However, differentiated cell populations still require purification following this process [51]. A number of studies have shown that faster, more efficient production of HE can be achieved through direct differentiation without the formation of EBs [52–57].

Bottom Line: The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality.The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes.Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, 49 Little France Crescent, Edinburgh,Scotland EH16 4SB, UK.

ABSTRACT
The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

Show MeSH
Related in: MedlinePlus