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.

<i>Cyba</i>-deficient mice display an increase in hematopoietic stem cells and an overproduction of immunoglobulins

“…ROS and NADPH oxidases are involved in the control of cell fate. 2 , 9–11 Hematopoiesis is a paradigmatic example of cell differentiation, because hematopoietic stem cells (HSC) must produce all mature blood lineages. There is increasing evidence suggesting the importance of redox signaling for hematopoietic differentiation, as well as for the contribution of an elevated level of ROS in the development of leukemia.…”

Differences in Mitochondrial Membrane Potential Identify Distinct Populations of Human Cardiac Mesenchymal Progenitor Cells

“…Knowing that metabolic switch during differentiation is dependent on increased mitochondrial activity [ 22 ], we have looked for mitochondrial biogenesis. We demonstrated an increase in cells with high Δψm of cytochrome c oxidase subunit 4I2 (COX4I2) and PGC-1α.…”

“…Indeed, low mitochondria number with reduced inner mitochondrial membrane potential (Δψm) and oxidative capacity [ 21 ], can explain for glycolytic metabolism of stem cells. Noteworthy, Δψm is now predictive of stem cell self-renewal and lineage commitment, providing a useful guide to select optimal stem cell population with enhanced stemness and/or differentiation capability for cellular therapy [ 22 ]. To date, very few studies were aimed at investigating the metabolism of resident hCmPCs [ 23 , 24 , 25 ].…”

“…To date, very few studies were aimed at investigating the metabolism of resident hCmPCs [ 23 , 24 , 25 ]. Here, for the first time, by TMRM, a fluorescent dye previously used to sort stem cells based on their Δψm [ 19 , 22 , 26 ], we identified two hCmPC populations characterized by different metabolic profile, stemness maturity and differentiation potential. Our findings suggest that metabolic sorting can complement sorting based on conventional cell surface markers in identifying cells with higher regenerative capacity and/or long-term survival with broader applicability in a variety of clinical settings.…”

Autophagy induction during stem cell activation plays a key role in salivary gland self-renewal

“…Most tissues with low or no proliferative steady-state properties, such as liver or skeletal muscle, respond to environmental changes, e.g ., tissue damage, upon which their stem cells become activated to expand, replace and therefore regenerate the tissue. The change from this quiescent, “dormant” state (naïve, low -activity stem cells) to an “activated” state (primed, proliferating stem cells) for regeneration, is accompanied by a change in both metabolism and gene expression [ 3 , 4 ].…”