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

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.

Octacalcium Phosphate for Bone Tissue Engineering: Synthesis, Modification, and In Vitro Biocompatibility Assessment

“…On the other hand, incubation of cells with all OCP-Sr for 96 h did not lead to an increase in the content of acidic compartments in the cells (Figure 6b). Additionally, to verify flow cytometry data, the content of acidic compartments and mitochondrial membrane potential in C3H/10T1/2 cells were examined using confocal microscopy after 96 h of co-incubation with OCP and OCP-Sr. For this, cells were stained Additionally, to verify flow cytometry data, the content of acidic compartments and mitochondrial membrane potential in C 3 H/10T1/2 cells were examined using confocal microscopy after 96 h of co-incubation with OCP and OCP-Sr. For this, cells were stained with LysoTracker Green and MitoTracker Red CMXRos [29]. H33342 was used to visualize the cell nucleus.…”

“…with LysoTracker Green and MitoTracker Red CMXRos [29]. H33342 was used to visualize the cell nucleus.…”

“…Additionally, to verify flow cytometry data, the content of acidic compartments and mitochondrial membrane potential in C 3 H/10T1/2 cells were examined using confocal microscopy after 96 h of co-incubation with OCP and OCP-Sr. For this, cells were stained with LysoTracker Green and MitoTracker Red CMXRos [ 29 ]. H33342 was used to visualize the cell nucleus.…”

Targeting PLD2 in adipocytes augments adaptive thermogenesis by improving mitochondrial quality and quantity in mice

“…4 K ). TMRM high cells have been shown to be efficient in terms of oxygen consumption rate (OCR), basal and maximal respiration, and spare respiratory capacity compared with TMRM low cells ( Choi et al, 2018 ; Franco-Iborra and Tanji, 2020 ; Gambini et al, 2020 ). In line with this, inhibition or depletion of PLD2 in brown adipocytes significantly enhanced the rate of oxygen consumption and the degree of oligomycin insensitive respiration ( Fig.…”

Transmission Electron Microscopy Reveals Propionic Acid-induced Alterations to Mitochondrial Morphology in SH-SY5Y Cells

“…Moreover, we also observed discrepancies in MitoTracker intensity across different cell populations under the same conditions (Figure 3). It has previously been shown that the degree of MitoTracker intensity is associated with distinct metabolic phenotypes within the same cell population [58]. This may be particularly true for cell populations that are undergoing dynamic metabolic remodeling in response to mild mitochondrial stress.…”