Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells

Xiao-hong Xu, Zhong Zhong
DOI: 10.1038/aps.2013.63


Xiao-hong XU1, 2, Zhong ZHONG2, *
1Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China; 2Regenerative Medicine DPU,
GlaxoSmithKline (China) R&D Co, Ltd, Shanghai 201203, China

With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors.

Keywords: induced pluripotent stem cells; embryonic stem cells; neurodegenerative diseases; disease modeling; drug screening

The authors would like to thank Jing ZHAO, Hai-yan FANG (both from GlaxoSmithKline R&D, China), Dwight MORROW (GlaxoSmithKline, USA), Kevin J KIM (Harvard Stem Cell Institute, USA) and Lucas CHASE (Cellular Dynamics International Inc, USA) for their critical reading of the manuscript and valuable suggestions.
* To whom correspondence should be addressed.
Received 2012-12-31 Accepted 2013-04-22

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