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Efficient generation of functional cardiomyocytes from human umbilical cord-derived virus-free induced pluripotent stem cells

  • Kai Hong Wu
  • Su Yun Wang
  • Qian Ru Xiao
  • Yu Yang
  • Ning Ping Huang
  • Xu Ming Mo
  • Jian Sun
Regular Article

Abstract

We have previously demonstrated that human umbilical cord-derived mesenchymal stem cells (UC-MSCs) can differentiate into cardiomyocyte-like cells. However, no contracting cells were observed during differentiation. In this study, we generated induced pluripotent stem cells (iPSCs) from UC-MSCs using mRNA reprogramming and focused on the differentiation of reprogrammed iPSCs into functional cardiomyocytes. For cardiac differentiation, the spontaneously contracting cell clusters were present on day 8 of differentiation. Immunostaining studies and cardiac-specific gene expression confirmed the cardiomyocyte phenotype of the differentiated cells. Electrophysiology studies indicated that iPSCs derived from UC-MSCs had a capacity for differentiation into nodal-, atrial-, and ventricular-like phenotypes based on action potential characteristics, and the derived cardiomyocytes exhibited responsiveness to β-adrenergic and muscarinic stimulations. Moreover, the derived cardiomyocytes displayed spontaneous intracellular Ca2+ transients. These results demonstrate that functional cardiomyocytes can be generated from reprogrammed UC-MSCs, and the methodology described here will serve as a useful protocol to obtain functional cardiomyocytes from human mesenchymal stem cells.

Keywords

Cardiomyocyte Differentiation Induced pluripotent stem cells Human umbilical cord Mesenchymal stem cells 

Notes

Funding information

This work was supported by the National Natural Science Foundation of China (grant no. 31671008), Medical Science and Technology Development Foundation, Jiangsu Provincial Commission of Health and Family Planning (grant no. ZDRCA2016073).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kai Hong Wu
    • 1
  • Su Yun Wang
    • 1
  • Qian Ru Xiao
    • 2
  • Yu Yang
    • 1
  • Ning Ping Huang
    • 2
  • Xu Ming Mo
    • 1
  • Jian Sun
    • 1
  1. 1.Cardiovascular CenterChildren’s Hospital of Nanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.State Key Laboratory of Bioelectronics, School of Biological Science and Medical EngineeringSoutheast UniversityNanjingPeople’s Republic of China

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