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Disease Modeling and Drug Discovery Using Human Pluripotent Stem Cells

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Stem Cells: Current Challenges and New Directions

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Cellular reprogramming and genome editing have enabled the generation of disease-specific human pluripotent stem cells for disease modeling and drug discovery. Although these cells have been heralded as a novel and invaluable tool for these application and numerous proof-of-principle studies have demonstrated their potential, there are still several challenges that have to be addressed in order for them to efficiently translate into drug discovery programs. In this chapter, we review some of the recent progress made in the field and also highlight the challenges that must be overcome in the use of human pluripotent stem cells to recapitulate human disease phenotypes and to screen for therapeutic agents in vitro.

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Abbreviations

ALS:

Amyloid lateral sclerosis

AMPK:

AMP-activated protein kinase

ARVD/C:

Arrhythmogenic right ventricular dysplasia/cardiomyopathy

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator

DA:

Dopaminergic

DCM:

Familial dilated cardiomyopathy

FD:

Familial dysautonomia

FAO:

Fatty acid oxidation

hESCs:

Human embryonic stem cells

hiPSCs:

Human-induced pluripotent stem cells

hPSCs:

Human pluripotent stem cells

HTS:

High-throughput screening

IGF1:

Insulin-like growth factor 1

IKBKAP :

I-κ-B kinase complex-associated protein

iPSCs:

Induced pluripotent stem cells

LNS:

Lesch-Nyhan syndrome

LQTS:

Long QT syndrome

MJD:

Machado-Joseph disease

PD:

Parkinson’s disease

RTT:

Rett syndrome

RSK:

Ribosomal S 6 kinase

Serca2a:

Sarcoplasmic reticulum calcium+ ATPase

SCZD:

Schizophrenia

SNCA :

α-Synuclein

SMA:

Spinal muscular atrophy

T1D:

Type 1 diabetes

XCI:

Inactive X chromosome

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Acknowledgements

The authors are members of the StemBANCC—Stem Cell for Drug Discovery consortium (www.stembancc.org). StemBANCC receives research funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115439, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies in kind contribution. www.imi.europa.eu. We thank Agnieszka Cecha for helping with the graphical design and Ole Dragsbæk Madsen for critical reading of the manuscript.

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  1. Hagedorn Research Institute, Novo Nordisk A/S, Niels Steensens vej 6, Gentofte, 2820, Denmark

    Christian Honoré & Mattias Hansson

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  1. Christian Honoré
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  2. Mattias Hansson
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Correspondence to Christian Honoré .

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  1. Regenerative Medicine Program, Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research, Ottawa, Ontario, Canada

    Kursad Turksen

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Honoré, C., Hansson, M. (2013). Disease Modeling and Drug Discovery Using Human Pluripotent Stem Cells. In: Turksen, K. (eds) Stem Cells: Current Challenges and New Directions. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8066-2_15

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