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Stem Cell Models

Stem cells are a promising method of producing a theoretically inexhaustible supply of hepatocytes from either embryonic or adult cells that can be used for toxicity testing or transplant. Embryonic stem cells (ESCs) are phenotypi-cally limited compared with iPSCs that can be derived from any individual. Given the wide array of phenotypes required to accurately predict idiosyncratic DILI, the wide array of phenotypes offered by iPSCs is a clear advantage. Therefore ESCs will not be the focus of this chapter instead it will focus on the development and use of iPSCs. iPSCs are derived from cells from adult donors and reverted to a plu-ripotent state, that is, able to enter any of the three germ layers. The iPSCs are subsequently differentiated into the cell type of interest such as HLCs (iPSC HLCs). [Pg.337]

APPLICATION OF PLURIPOTENT STEM CELLS IN DRUG-INDUCED LIVER INJURY SAFETY ASSESSMENT [Pg.338]

The first integration-free iPSCs were produced using a replication-defective adenoviral vector, where OSKM factors were delivered by separate vectors (Stadtfeld et al., 2008). F-deficient Sendai virus has also been used to deliver transgenes to a wide array of host cells where it replicates as negative-sense ssRNA, the virus is diluted out after multiple passages, and the loss of the virus can be confirmed by PCR (Fusaki et al., 2009 Nishimura etal., 2011). [Pg.338]

Reprogramming has recently been demonstrated in murine cells using a cocktail of small molecules (Hou et al., 2013). This approach shows great promise in that genetic manipulation of the cells is entirely avoided with no risky expression of potent oncogenes. However, the efficiency of reprogramming is low and thus far has not been replicated in human cells. [Pg.338]


Przyborski SA, Christie VB, Hayman MW, Stewart R, Horrocks GM (2004) Human embryonal carcinoma stem cells models of embryonic development in humans. Stem Cells Dev 13 400-408... [Pg.142]

Shi, Y., Kirwan, P., Smith, J., et al. A Human Stem Cell Model of Early Alzheimer s Disease Pathology in Down Syndrome. Sci. Transl. Med. 4, 1-9 (2012)... [Pg.319]

Davis, R.R, van den Berg, C.W., Casini, S., Braam, S.R., and Mummery, C.L. (2011) Pluripotent stem cell models of cardiac disease and their implication for drug discovery and development. Trends Mol. Med. 17, 475 84. [Pg.289]

A. Moretti, M. Beilin, A. Welling, C. B. Jung, J. T. Lam, L. Bott-Flugel, T. Dom, A. Goedel, C. Hohnke, F. Hofmann, Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363,1397—1409 (2010). [Pg.362]

Morizane R, Lam AQ, Freedman BS, Kishi S, Valerius MT, Bonventre JV. 2015. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol 33(11) 1193-1200. [Pg.382]

Carter, RX., and Chan, A.W. (2012) Pluripotent stem cells models for Huntington s disease prospects and challenges. Journal of Genetics and Genomics, 39,253-259. [Pg.304]

Miki, J and JS Rhim. 2007. Prostate cell cultures as in vitro models for the study of normal stem cells and cancer stem cells. Prostate Cancer Prostatic Dis 11(1 ) 32—39. [Pg.462]

McIntosh KR et al (2009) hnmunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Eng Part A 15(9) 2677-2686... [Pg.229]

An important controversy remains about which factors, intrinsic or extrinsic, control the stem cell s decision to self-renew or develop into one of several committed progenitor cells. Two distinct models have been proposed to... [Pg.504]


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