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The Low Tumorigenic Risk and Subtypes of Cardiomyocytes Derived from Human-induced Pluripotent Stem Cells

Jizhen Lu1, Lu Zhang1, Hongxia Cao1

  • 1National Stem Cell Translational Resource Center/GMP Laboratory of Stem Cell Transformation Medicine Industry Base, Shanghai East Hospital (East Hospital Affiliated to Tongji University), Tongji University School of Life Sciences and Technology, Shanghai, People's Republic of China.

Current Stem Cell Research & Therapy
|May 12, 2025
PubMed

Insights

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show no tumorigenicity and possess distinct cardiac subtypes. This research provides crucial safety data and characterization for clinical heart disease treatments.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Therapy
  • Regenerative Medicine

Background:

  • Clinical translation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is hindered by tumorigenicity concerns.
  • Accurate identification of hiPSC-CM subtypes is essential for safe and effective cardiac disease treatments.

Purpose of the Study:

  • To evaluate the biological safety and characterize the subtypes of hiPSC-CMs for clinical applications.
  • To establish quality control standards for hiPSC-CMs.

Main Methods:

  • hiPSC-CMs were generated using Wnt signaling modulation and glucose deprivation.
  • Single-cell RNA sequencing (scRNAseq), whole exome sequencing (WES), and in vivo transplantation were employed.
  • Flow cytometry, molecular biology, and electrophysiology techniques were utilized for comprehensive analysis.

Main Results:

  • High purity hiPSC-CMs were generated, with scRNAseq confirming the absence of undifferentiated hiPSC markers.
  • Whole exome sequencing revealed minimal new mutations, and no tumor formation was observed in mice post-transplantation.
  • hiPSC-CMs comprised ventricular-like (23.19%) and atrial-like (66.45%) subtypes, including mature ventricular cells and early-stage cells undergoing apoptosis.

Conclusions:

  • This study confirms the biological safety of hiPSC-CMs, mitigating tumorigenicity concerns.
  • Detailed characterization of cardiac subtypes and their expression profiles provides essential quality control standards.
  • Findings support the translational application of hiPSC-CMs in treating heart diseases.
Abstract

Keywords:
cardiac subtypescardiomyocyteshiPSCsingle-cell RNA sequencetumorigenicity.whole exome sequence

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