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iPS Cells and Cardiomyopathies

  • Chapter
Stem Cells in Modeling Human Genetic Diseases

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

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Abstract

The advent of induced pluripotent stem cells (iPSC) revolutionized the approach of studying cardiac diseases and development. The iPSC technology allows the generation of human cardiac platforms in vitro that can be used for modeling a disease of interest, for testing and discovering novel therapeutics. Furthermore, the possibility of generating genetically matched human cardiac progenitor cells and cardiomyocytes (CMs) have much potential in regenerative medicine. This chapter provides an overview of the cardiac models that have been developed thus far using iPSC and will entail: first, their advantages over other existing models; second, the impact of this technology for the understanding of pathogenesis of cardiac diseases with a particular focus on cardiomyopathies; and third, the importance of development of genome-editing strategies for the causal definition of mechanisms of diseases. In addition, how this gain of knowledge correlates with the development of novel therapeutic options for disease treatment and possible cure will also be discussed.

A small section is also dedicated to the methods for generating CMs from iPSC and to the advances that have been made to obtain pure populations of cardiac cells at high efficiency. Finally to conclude, a perspective of the current limitations, which will be the key to overcoming barriers to enter the clinical practice, will be addressed.

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Abbreviations

AAVS1:

Adeno-associated virus integration site 1

AFM:

Atomic force microscopy

ANF:

Atrial natriuretic factor

AP:

Action potential

APD:

Action potential duration

ARVD/C:

Arrhythmogenic right ventricular dysplasia/cardiomyopathy

bFGF:

Basic fibroblast growth factor

BMP2:

Bone morphogenic protein 2

bpm:

Beats per minute

BTHS:

Barth syndrome

CACNA1C:

Calcium Channel, Voltage-Dependent, L Type, Alpha 1C Subunit

CASQ2:

Calsequestrin gene

CMs:

Cardiomyocytes

CNX43:

Connexin 43

CPVT:

Catecholaminergic polymorphic ventricular tachycardia

CRISPR:

Clustered regularly inter-spaced short palindromic repeats

CsA:

Cyclosporin A

DADs:

Delayed afterdepolarizations

DCM:

Dilated cardiomyopathy

DES:

Desmin gene

Dkk-1:

Dickkopf-related protein

DSBs:

Double-strand DNA cleavage

EADs:

Early-afterdepolarization

EBs:

Embryoid bodies

END2:

Visceral endoderm-like cells

ESCs:

Embryonic stem cells

ET-1:

Endothelin-1

FPD:

Field potential duration

FRDA:

Friedreich ataxia

FXN:

Fataxin gene

GAA:

Acid-α-glucosidase

GATA4:

GATA binding protein 4

HCM:

Hypertrophic cardiomyopathy

HDAd:

Helper-dependent adenoviral vectors

HR:

Homologous Recombination

IFNβ1:

Interferon beta 1

iPSC:

Induced pluripotent stem cells

iPSC-CMs:

iPSC-derived cardiomyocytes

KCNH2:

Potassium voltage-gated channel, subfamily H (Eag-related), member 2

KCNJ2:

Potassium inwardly rectifying channel, subfamily J, Member 2

KCNQ1:

Potassium voltage-gated channel, KQT-like subfamily, member 1

LAMP:

Lysosome-associated membrane protein

LQT:

Long QT syndrome

MEA:

Multi-electrode array

MEF2C:

Myocyte enhancer factor 2C

MHY7:

Beta-myosin heavy chain gene

MYL2:

Myosin, light chain 2, regulatory, cardiac, slow

NE:

Norepinephrine

NFAT:

Nuclear factor of activated T cells

NHEJ:

Nonhomologous end joining

PDTC:

Pyrrolidine dithiocarbamate

Pkp2:

Plakophilin-2 gene

PPARγ:

Peroxisome proliferator-activated receptor-gamma

PTPN11:

Protein tyrosine phosphatase, non-receptor type 11

RCM:

Restrictive cardiomyopathy

RNAi:

RNA interference

Ros:

Roscovitine

RYR2:

Ryanodine receptor gene

SCN5A:

Sodium channel, voltage-gated, type V, alpha subunit

Serca2a:

Sarcoplasmic reticulum Ca2+ ATPase

sgRNA:

Single chimeric guide RNA

ssODNs:

Single-strand DNA oligonucleotides

TALEN:

Transcription activator-like effector nuclease

TAZ:

Tafazzin

TGFβ:

Transforming growth factor beta

TNNT2:

Cardiac troponin T gene

VEGF:

Vascular endothelial growth factor

ZFN:

Zinc finger nucleases

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Authors and Affiliations

  1. Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Hiroko Nakahama & Elisa Di Pasquale

  2. CNR—Institute of Genetic and Biomedical Research, UOS of Milan, Via Manzoni 113, Rozzano, Milan, 20089, Italy

    Elisa Di Pasquale

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  1. Hiroko Nakahama
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  2. Elisa Di Pasquale
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Correspondence to Elisa Di Pasquale .

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  1. Human Genome and Stem-Cell center(HUG-CELL), Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

    Mayana Zatz

  2. Human Genome and Stem-Cell center(HUG-CELL),Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

    Oswaldo Keith Okamoto

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Nakahama, H., Di Pasquale, E. (2015). iPS Cells and Cardiomyopathies. In: Zatz, M., Keith Okamoto, O. (eds) Stem Cells in Modeling Human Genetic Diseases. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-18314-5_6

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