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Related Experiment Video

Updated: Jun 20, 2026

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
05:38

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells

Published on: February 12, 2021

iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism.

Almudena Martinez-Fernandez1, Timothy J Nelson, Satsuki Yamada

  • 1Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, Minn. 55905, USA.

Circulation Research
|August 22, 2009
PubMed
Summary

Induced pluripotent stem cells (iPS) reprogrammed without c-MYC demonstrate robust cardiac differentiation. These three-factor iPS (3F-iPS) yield de novo heart tissue compatible with native counterparts from embryo to adulthood.

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Area of Science:

  • Stem Cell Biology
  • Developmental Biology
  • Cardiovascular Research

Background:

  • Induced pluripotent stem cells (iPS) offer a route to generate pluripotent progenitors from somatic cells.
  • Traditional iPS induction utilized a gene set including the c-MYC oncogene.
  • The role of c-MYC in cardiogenesis remained a key question.

Purpose of the Study:

  • To investigate the cardiogenic potential of iPS programmed without c-MYC.
  • To assess the differentiation capabilities of these modified iPS from embryonic to adult stages.

Main Methods:

  • Fibroblasts were reprogrammed into iPS using three factors (SOX2, OCT4, KLF4) without c-MYC.
  • Cardiac differentiation was assessed through embryoid body formation and expression of cardiac markers.
  • In vivo studies involved morula-stage aggregation and assessment of cardiac development in chimeric offspring.

Main Results:

  • Three-factor iPS (3F-iPS) exhibited pluripotency markers and generated three germ layers.
  • 3F-iPS clones showed vigorous cardiac differentiation, including beating embryoid bodies and expression of key cardiac proteins (Mef2c, alpha-actinin, connexin43, MLC2a, troponin I).
  • In vitro cardiomyocytes displayed functional excitation-contraction coupling, and in vivo studies confirmed sustained chimerism and normal cardiac development in adult offspring.

Conclusions:

  • iPS programmed without c-MYC meet stringent criteria for bona fide cardiogenesis.
  • This approach enables reprogrammed fibroblasts to generate de novo heart tissue.
  • The resulting cardiac tissue is compatible with native counterparts throughout development and into adulthood.