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New Approaches in the Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells toward Hepatocytes

Transplant Research Program, Department of Internal Medicine, University of California Davis Medical Center, 4635 2nd Ave. Suite 1001, Sacramento, CA 95817, USA.
Stem cell reviews (Impact Factor: 3.21). 02/2011; 7(3):748-59. DOI: 10.1007/s12015-010-9216-4
Source: PubMed

ABSTRACT Orthotropic liver transplantation is the only established treatment for end-stage liver diseases. Utilization of hepatocyte transplantation and bio-artificial liver devices as alternative therapeutic approaches requires an unlimited source of hepatocytes. Stem cells, especially embryonic stem cells, possessing the ability to produce functional hepatocytes for clinical applications and drug development, may provide the answer to this problem. New discoveries in the mechanisms of liver development and the emergence of induced pluripotent stem cells in 2006 have provided novel insights into hepatocyte differentiation and the use of stem cells for therapeutic applications. This review is aimed towards providing scientists and physicians with the latest advancements in this rapidly progressing field.

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Available from: Tijess P Ahuja, Jul 08, 2015
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    • "Assessment of hepatotoxicity remains difficult because of challenges associated with in vivo models [3] and the high cost and limited availability of liver tissue for in vitro studies [4]. Current in vitro models for assessing hepatotoxicity are limited by (a) scarcity, variability, and short life span in culture of primary human hepatocytes [4]; (b) lack of metabolic activity in widely used liver cell lines such as HepG2 [5]; and (c) the complex long-term protocols required to differentiate progenitor cells [6]. "
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    • "Also, the utility of primary hepatocytes as a therapy is hindered by their antigenicity, slow growth, loss of function and de-differentiation in vitro. Human embryonic stem cells (hESCs) or human induced pluripotent stem cells (iPSCs), which possess the ability to provide an unlimited source to generate human hepatocytes, could provide an answer to this problem [1] [2] [3]. Moreover, use of iPSCs would circumvent ethical issues, and, in particular, use of iPSCs derived from the same patient would overcome immunological rejection. "
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    ABSTRACT: Background Human induced pluripotent stem cells, which can be differentiated into hepatocyte-like cells, could provide a source for liver regeneration and bio-artificial liver devices. However, the functionality of hepatocyte-like cells is significantly lower than that of primary hepatocytes. Aims To investigate whether serum from patients undergoing hepatectomy might promote differentiation from human induced pluripotent stem cells to hepatocyte-like cells. Methods Serum from patients undergoing hepatectomy (acquired pre-hepatectomy and 3 hours, 1 day and 3 days post-hepatectomy) was used to replace foetal bovine serum when differentiating human induced pluripotent stem cells into hepatocyte-like cells. Properties of hepatocyte-like cells were assessed and compared with cells cultured in foetal bovine serum. Results The differentiation efficiency and functionality of hepatocyte-like cells cultured in human serum 3 hours and 1 day post-hepatectomy were superior to those cultured in foetal bovine serum and human serum pre-hepatectomy. Human serum 3 days post-hepatectomy had an equal effect to that of human serum pre-hepatectomy. Some cytochrome P450 isozyme transcript levels of hepatocyte-like cells cultured in human serum were higher than those cultured in foetal bovine serum. Conclusion Human serum, particularly that acquired relatively soon after hepatectomy, can enhance the differentiation efficiency and functionality of hepatocyte-like cells derived from human induced pluripotent stem cells.
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