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Derivation of Highly Purified Cardiomyocytes from Human Induced Pluripotent Stem Cells Using Small Molecule-modulated Differentiation and Subsequent Glucose Starvation
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Derivation of Highly Purified Cardiomyocytes from Human Induced Pluripotent Stem Cells Using Small Molecule-modulated Differentiation and Subsequent Glucose Starvation

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Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects

Xi Jiang1, Xin Lian2, Kun Wei3

  • 1Health management center, the First Hospital of Jilin University, Changchun, China.

Stem Cell Research & Therapy
|October 8, 2024
PubMed

Insights

Human induced pluripotent stem cells (hiPSCs) can regenerate heart muscle but have immature metabolism. Improving hiPSC-cardiomyocyte metabolism is key for effective cardiac repair after myocardial infarction.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Biology
  • Metabolic Engineering

Background:

  • Acute coronary syndromes, including myocardial infarction (MI), have limited treatment options beyond heart transplantation.
  • Human induced pluripotent stem cells (hiPSCs) offer potential for myocardial regeneration by differentiating into cardiomyocytes.
  • hiPSC-derived cardiomyocytes (hiPSC-cardiomyocytes) display immature metabolic and calcium handling properties, hindering effective engraftment and therapeutic efficacy.

Purpose of the Study:

  • To review the impact of mitochondrial biogenesis and metabolic switching on hiPSC-cardiomyocyte maturation.
  • To discuss current limitations in assessing hiPSC-cardiomyocyte metabolism.
  • To highlight challenges in achieving adult-like metabolic flexibility in hiPSC-cardiomyocytes for cardiac repair.

Main Methods:

  • Literature review focusing on mitochondrial function, metabolic pathways, and maturation processes in hiPSC-cardiomyocytes.
  • Analysis of strategies aimed at enhancing energy substrate utilization and improving the transplantation microenvironment.
  • Examination of methodologies for metabolic assessment in hiPSC-cardiomyocytes.

Main Results:

  • Altered mitochondrial biogenesis and metabolic switching significantly influence hiPSC-cardiomyocyte maturation.
  • Current assessment methods for hiPSC-cardiomyocyte metabolism have inherent limitations.
  • Achieving metabolic flexibility comparable to adult cardiomyocytes remains a significant challenge.

Conclusions:

  • Metabolic maturation is critical for the successful therapeutic application of hiPSC-cardiomyocytes in treating heart disease.
  • Further research is needed to overcome metabolic immaturity and enhance the clinical potential of hiPSC-cardiomyocytes for cardiac regeneration.
  • Optimizing metabolic function is essential for improving hiPSC-cardiomyocyte engraftment and long-term efficacy in myocardial repair.

Keywords:
Acute coronary syndromesEnergy metabolismInduced pluripotent stem cellsMaturationMyocardial infarctioniPSC-cardiomyocytes

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