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Modeling Cardiovascular Diseases with Patient-Specific Human Pluripotent Stem Cell-Derived Cardiomyocytes

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Patient-Specific Induced Pluripotent Stem Cell Models

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1353))

Abstract

The generation of cardiomyocytes from human induced pluripotent stem cells (hiPSCs) provides a source of cells that accurately recapitulate the human cardiac pathophysiology. The application of these cells allows for modeling of cardiovascular diseases, providing a novel understanding of human disease mechanisms and assessment of therapies. Here, we describe a stepwise protocol developed in our laboratory for the generation of hiPSCs from patients with a specific disease phenotype, long-term hiPSC culture and cryopreservation, differentiation of hiPSCs to cardiomyocytes, and assessment of disease phenotypes. Our protocol combines a number of innovative tools that include a codon-optimized mini intronic plasmid (CoMiP), chemically defined culture conditions to achieve high efficiencies of reprogramming and differentiation, and calcium imaging for assessment of cardiomyocyte phenotypes. Thus, this protocol provides a complete guide to use a patient cohort on a testable cardiomyocyte platform for pharmacological drug assessment.

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References

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Acknowledgements

This work was supported by the American Heart Association Beginning Grant-in-Aid 14BGIA20480329 and US National Institutes of Health K99 HL121177 to P.W.B.; American Heart Association Predoctoral Fellowship 13PRE15770000, National Science Foundation Graduate Research Fellowship Program DGE-114747 to A.S.; American Heart Association Established Investigator Award 14420025, Foundation Leducq, the National Institutes of Health U01 HL099776, P01 GM099130, R01 HL113006, R01 HL123968, and R24 HL117756 to J.C.W.

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Authors and Affiliations

  1. Department of Medicine (Division of Cardiology), Stanford Cardiovascular Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Paul W. Burridge Ph.D., Elena Matsa, Arun Sharma & Haodi Wu

  2. Department of Medicine (Division of Cardiology), Stanford Cardiovascular Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA, 94305-5454, USA

    Joseph C. Wu M.D., Ph.D.

  3. Max Delbrück Center, Berlin Institute of Health, Berlin, Germany

    Sebastian Diecke

Authors
  1. Paul W. Burridge Ph.D.
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  2. Sebastian Diecke
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  3. Elena Matsa
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  4. Arun Sharma
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  5. Haodi Wu
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  6. Joseph C. Wu M.D., Ph.D.
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Corresponding author

Correspondence to Joseph C. Wu M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada

    Andras Nagy

  2. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Kursad Turksen

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© 2015 Springer Science+Business Media New York

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Burridge, P.W., Diecke, S., Matsa, E., Sharma, A., Wu, H., Wu, J.C. (2015). Modeling Cardiovascular Diseases with Patient-Specific Human Pluripotent Stem Cell-Derived Cardiomyocytes. In: Nagy, A., Turksen, K. (eds) Patient-Specific Induced Pluripotent Stem Cell Models. Methods in Molecular Biology, vol 1353. Humana Press, New York, NY. https://doi.org/10.1007/7651_2015_196

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  • DOI: https://doi.org/10.1007/7651_2015_196

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3033-3

  • Online ISBN: 978-1-4939-3034-0

  • eBook Packages: Springer Protocols

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