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Bioengineered Cardiac Tissue Based on Human Stem Cells for Clinical Application

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  • First Online:
Engineering and Application of Pluripotent Stem Cells

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 163))

Abstract

Engineered cardiac tissue might enable novel therapeutic strategies for the human heart in a number of acquired and congenital diseases. With recent advances in stem cell technologies, namely the availability of pluripotent stem cells, the generation of potentially autologous tissue grafts has become a realistic option. Nevertheless, a number of limitations still have to be addressed before clinical application of engineered cardiac tissue based on human stem cells can be realized. We summarize current progress and pending challenges regarding the optimal cell source, cardiomyogenic lineage specification, purification, safety of genetic cell engineering, and genomic stability. Cardiac cells should be combined with clinical grade scaffold materials for generation of functional myocardial tissue in vitro. Scale-up to clinically relevant dimensions is mandatory, and tissue vascularization is most probably required both for preclinical in vivo testing in suitable large animal models and for clinical application.

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Abbreviations

AAVS1:

Adeno-associated virus integration site (safe harbor site)

ABCG2:

ATP-binding cassette transporter protein

AMI:

Acute myocardial infarction

ARVCM:

Arrythmogenic right ventricular cardiomyopathy

ASC:

Adipose tissue-derived cell

AV-block:

Atrioventricular block

AV-node:

Atrioventricular node

BCRP:

Breast cancer resistance protein

BMP:

Bone morphogenic protein

CD117:

c-kit

CD106/VCAM-1:

Vascular cell adhesion molecule 1

CD166/ALCAM:

Activated leukocyte cell adhesion molecule

CD172A/SIRP-alpha:

Signal regulatory protein alpha

CDC:

Cardiosphere-derived cell

CMPM:

Cardiac myocyte-populated matrix

c-Myc:

Avian myelocytomatosis viral oncogene homolog

COUP-TF I and II:

Chicken ovalbumin upstream promoter transcription factor I and II

CRISPR/Cas9:

Clustered regularly interspaced short palindromic repeats/CRISPR-associated system

CRPC:

Cardiac resident progenitor cell

CTLA4:

Cytotoxic T-lymphocyte-associated protein 4

DNA:

Deoxyribonucleic acid

EBIO:

1-Ethyl-2-benzimidazolinone

ECM:

Extracellular matrix

eGFP:

Enhanced green fluorescent protein

EHT:

Engineered heart tissue

ESC:

Embryonic stem cell

FACS:

Fluorescence-activated cell sorting

FGF-16:

Fibroblast growth factor 16

GATA4:

GATA-binding protein 4

GFP:

Green fluorescent protein

hESC:

Human embryonic stem cell

hiPSC:

Human induced pluripotent stem cell

HUVEC:

Human umbilical vein endothelial cell

ICF:

Immunodeficiency, centromeric region instability, facial anomalies

iPSC:

Induced pluripotent stem cell

IWP:

Inhibitor of Wnt production

Klf4:

Kruppel-like factor 4

linneg/c-kitpos :

CD31, CD34, CD45 negative/CD117 positive

LVEF:

left ventricular ejection fraction

Meis-1:

Meis homeobox 1

miR-128:

micro RNA 128

MLC2a:

Myosin light chain 2a

MLC2v:

Myosin light chain 2v

MRI:

Magnetic resonance imaging

MSC:

Mesenchymal stem cell

MYDGF:

Myeloid-derived growth factor

Nkx2.5:

NK2 homeobox 5

NRCM:

Neonatal rat cardiomyocytes

NRG1β/ERBB:

Neuregulin 1/estrogen receptor beta

Oct4:

Octamer-binding protein 4

p38 MAPK:

p38 mitogen-activated protein kinase

PCR:

Polymerase chain reaction

PDGFRβ:

Platelet-derived growth factor receptor β

PSC:

Pluripotent stem cell

RGD:

Arginyl-glycyl-aspartic acid motif

sca-1:

Stem cell antigen-1

Sox2:

Sex determining region Y-box 2

SP:

Side population

TALEN:

TAL effector nuclease

TnI:

Troponin I

USSC:

Unrestricted somatic stem cell

VSD:

Ventricular septal defect

Wnt:

Wingless protein

ZFN:

Zinc-finger nuclease

α-MHC, MYH6:

α-myosin heavy chain promoter

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Acknowledgments

We thank Sylvia Merkert for help with TALEN-mediated targeted transgene integration into the AAVS1 locus and Anke Gawol for the generation of clonal iPSC lines.

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Authors and Affiliations

  1. Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department for Cardiothoracic, Vascular and Transplantation Surgery (HTTG), Hannover Medical School (MHH) & Cluster of Excellence REBIRTH, Hannover, Germany

    Monica Jara Avaca & Ina Gruh

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  1. Monica Jara Avaca
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  2. Ina Gruh
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Correspondence to Ina Gruh .

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  1. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Ulrich Martin

  2. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Robert Zweigerdt

  3. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Ina Gruh

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Jara Avaca, M., Gruh, I. (2017). Bioengineered Cardiac Tissue Based on Human Stem Cells for Clinical Application. In: Martin, U., Zweigerdt, R., Gruh, I. (eds) Engineering and Application of Pluripotent Stem Cells. Advances in Biochemical Engineering/Biotechnology, vol 163. Springer, Cham. https://doi.org/10.1007/10_2017_24

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