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Updated: Dec 6, 2025
Isolation of Perivascular Multipotent Precursor Cell Populations from Human Cardiac Tissue
Published on: October 8, 2016
Differences in Mitochondrial Membrane Potential Identify Distinct Populations of Human Cardiac Mesenchymal Progenitor
Elisa Gambini1, Ilenia Martinelli2, Ilaria Stadiotti1
1Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138 Milan, Italy.
Insights
Researchers identified two distinct populations of human cardiac progenitor cells based on their mitochondrial function. This metabolic sorting method can isolate cells with improved regenerative potential for cardiac repair therapies.
Area of Science:
- Cardiology
- Stem Cell Biology
- Mitochondrial Metabolism
Background:
- Adult human cardiac progenitor cells (hCmPCs) are crucial for heart repair, but their differentiation is influenced by mitochondrial metabolism.
- Current methods do not effectively identify hCmPCs with superior stemness or differentiation capabilities for cellular therapy.
Purpose of the Study:
- To investigate if mitochondrial membrane potential can be used to sort hCmPCs with distinct metabolic profiles and functional properties.
- To explore the relationship between mitochondrial metabolism and stemness/differentiation potential in hCmPCs.
Main Methods:
- Human cardiac progenitor cells (hCmPCs) were sorted into low and high mitochondrial membrane potential groups using tetramethylrhodamine methyl ester (TMRM).
- Differences in energy metabolism, including glycolysis and oxidative respiration, were analyzed between the sorted cell populations.
- In vitro differentiation capacity and self-renewal potential were assessed for both TMRM-low and TMRM-high cells.
Main Results:
- TMRM-high hCmPCs exhibited higher oxygen consumption, basal and maximal respiration, and spare respiratory capacity, indicating a more oxidative metabolism.
- TMRM-high cells showed enhanced in vitro differentiation into endothelial and cardiac-like lineages, with some adipogenic and chondro/osteogenic potential.
- TMRM-low hCmPCs demonstrated a greater capacity for self-renewal.
Conclusions:
- Two distinct hCmPC populations with differing metabolic profiles, stemness maturity, and differentiation potentials were identified.
- Metabolic sorting based on mitochondrial membrane potential can isolate cells with enhanced regenerative capacity and long-term survival.
- This metabolism-based cell selection strategy holds broad applicability for regenerative medicine and cardiac therapies.
Abstract:
Adult human cardiac mesenchymal progenitor cells (hCmPC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Even if the mechanisms have not yet been fully elucidated, the stem cell differentiation is guided by the mitochondrial metabolism; however, mitochondrial approaches to identify hCmPC with enhanced stemness and/or differentiation capability for cellular therapy are not established. Here we demonstrated that hCmPCs sorted for low and high mitochondrial membrane potential (using a lipophilic cationic dye tetramethylrhodamine methyl ester, TMRM), presented differences in energy metabolism from preferential glycolysis to oxidative rates. TMRM-high cells are highly efficient in terms of oxygen consumption rate, basal and maximal respiration, and spare respiratory capacity compared to TMRM-low cells. TMRM-high cells showed characteristics of pre-committed cells and were associated with higher in vitro differentiation capacity through endothelial, cardiac-like, and, to a lesser extent, adipogenic and chondro/osteogenic cell lineage, when compared with TMRM-low cells. Conversely, TMRM-low showed higher self-renewal potential. To conclude, we identified two hCmPC populations with different metabolic profile, stemness maturity, and differentiation potential. Our findings suggest that metabolic sorting can isolate cells with higher regenerative capacity and/or long-term survival. This metabolism-based strategy to select cells may be broadly applicable to therapies.
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