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Induced pluripotent stem cells: developmental biology to regenerative medicine

Nature Reviews Cardiology volume 7, pages 700–710 (2010)Cite this article

Subjects

Abstract

Nuclear reprogramming of somatic cells with ectopic stemness factors to bioengineer pluripotent autologous stem cells signals a new era in regenerative medicine. The study of developmental biology has provided a roadmap for cardiac differentiation from embryonic tissue formation to adult heart muscle rejuvenation. Understanding the molecular mechanisms of stem-cell-derived cardiogenesis enables the reproducible generation, isolation, and monitoring of progenitors that have the capacity to recapitulate embryogenesis and differentiate into mature cardiac tissue. With the advent of induced pluripotent stem (iPS) cell technology, patient-specific stem cells provide a reference point to systematically decipher cardiogenic differentiation through discrete stages of development. Interrogation of iPS cells and their progeny from selected cohorts of patients is an innovative approach towards uncovering the molecular mechanisms of disease. Thus, the principles of cardiogenesis can now be applied to regenerative medicine in order to optimize personalized therapeutics, diagnostics, and discovery-based science for the development of novel clinical applications.

Key Points

  • Induced pluripotent stem (iPS) cells are autologous, somatic cells that have been modified to acquire an embryonic stem-cell-like capacity

  • iPS cells enable patient-specific examination of the molecular mechanisms of health and disease, and provide cell-based platforms for personalized diagnostics and therapeutics

  • iPS-cell-derived progeny have the potential to closely recapitulate natural cardiogenic differentiation

  • Nuclear reprogramming involves embryo-independent generation of iPS cells with ectopic stemness factors, which resets the fate of the cell to a self-sustainable pluripotent state

  • Various strategies are used for nuclear reprogramming, including genetic engineering with viruses, traceless systems, and genomic-free approaches

  • Bioengineered clones must undergo stringency testing to validate their functionality as iPS cells

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Figure 1: iPS cells for personalized theranostics.
Figure 2: A tool kit for inducing pluripotency.
Figure 3: Strategies to optimize nuclear reprogramming.
Figure 4: Stringency testing for iPS cells.
Figure 5: Bioengineered cardiogenesis for applications in cardiovascular regenerative medicine.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Medicine, Marriott Heart Disease Research Program, Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA

    Timothy J. Nelson, Almudena Martinez-Fernandez & Andre Terzic

Authors
  1. Timothy J. Nelson
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  2. Almudena Martinez-Fernandez
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  3. Andre Terzic
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Contributions

T. J. Nelson and A. Terzic contributed to discussion of content for the article, researched data to include in the manuscript, wrote the manuscript, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments. A. Martinez-Fernandez contributed to discussion of content for the article, researched data to include in the manuscript, and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Timothy J. Nelson.

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The authors declare no competing financial interests.

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Nelson, T., Martinez-Fernandez, A. & Terzic, A. Induced pluripotent stem cells: developmental biology to regenerative medicine. Nat Rev Cardiol 7, 700–710 (2010). https://doi.org/10.1038/nrcardio.2010.159

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