Addressing Variability and Heterogeneity of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

  • Sherri M. Biendarra-Tiegs
  • Frank J. Secreto
  • Timothy J. NelsonEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1212)


Induced pluripotent stem cells (iPSCs) offer great promise in the areas of disease modeling, basic research, drug development, and regenerative medicine. Much of their value comes from the fact that they can be used to create otherwise inaccessible cell types, such as cardiomyocytes, which are genetically matched to a patient or any other individual of interest. A consistent issue plaguing the iPSC platform, however, involves excessive variability exhibited in the differentiated products. This includes discrepancies in genetic, epigenetic, and transcriptional features, cell signalling, the cell types produced from cardiac differentiation, and cardiomyocyte functionality. These properties can result from both the somatic source cells and environmental conditions related to the derivation and handling of these cells. Understanding the potential sources of variability, along with determining which factors are most relevant to a given application, are essential in advancing iPSC-based technologies.


Cardiomyocytes Cellular microenvironment Differentiation Induced pluripotent stem cells Phenotypic variability Stem cell heterogeneity 



action potential


action potential duration


current Good Manufacturing Practice


copy number variation


differentially expressed gene


embryoid body


extracellular matrix


etoposide sensitivity assay


embryonic stem cell


embryonic stem cell-derived cardiomyocyte


fluorescence-activated cell sorting


induced pluripotent stem cell


induced pluripotent stem cell-derived cardiomyocyte


mitochondrial DNA


single nucleotide variation


X-chromosome inactivation



This work was supported by the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome at Mayo Clinic. Figures were created with BioRender.

Conflict of interest

T.J.N and Mayo Clinic have licensed reprogramming technology to ReGen Theranostics, Inc. in Rochester, MN.

Ethical approval

The authors declare that this article does not contain any studies with human participants or animals.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sherri M. Biendarra-Tiegs
    • 1
    • 2
  • Frank J. Secreto
    • 2
    • 3
  • Timothy J. Nelson
    • 1
    • 2
    • 4
    • 5
    • 3
    Email author
  1. 1.Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterUSA
  2. 2.Program for Hypoplastic Left Heart Syndrome-Center for Regenerative MedicineMayo ClinicRochesterUSA
  3. 3.Department of Internal Medicine, Division of General Internal MedicineMayo ClinicRochesterUSA
  4. 4.Department of Cardiovascular MedicineMayo ClinicRochesterUSA
  5. 5.Department of Pediatric and Adolescent Medicine, Division of Pediatric CardiologyMayo ClinicRochesterUSA

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