Eat, breathe, ROS: controlling stem cell fate through metabolism

ABSTRACT

Introduction: Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood.

Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement.

Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

KEYWORDS:

• Cardiac progenitor cell
• differentiation
• glycolysis
• metabolism
• mitochondria
• pluripotency
• reactive oxygen species
• respiration
• self-renewal
• stem cell

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

D.A Kubli is supported by the National Institutes of Health (grant number: F32HL136064. M.A. Sussman is supported by the National Institutes of Health (grant numbers: R01HL067245, R37HL091102, R01HL105759, R01HL113647, R01HL117163, P01HL085577 and R01HL122525) as well as an award from the Fondation Leducq.