Cardiosphere-Derived Cells from Not Dilated and Dilated Human Myocardium Exhibit Enhanced Metabolic Potential Compared with Conventional Cardiac Mesenchymal Stem/Stromal Cells.

Dilated cardiomyopathy (DCM) is a major contributor to heart failure and cardiac transplantation. This study investigated the metabolic potential of human myocardium-derived mesenchymal stem/stromal cells (hmMSCs) and subsequently cardiac sphere-derived cells (SDCs) obtained from healthy (non-dilated) and pathological (dilated) myocardial tissues. hmMSCs were isolated using the explant outgrowth method and expanded in monolayer culture. Small round cells loosely attached on hmMSCs were harvested and cultivated as cardiac spheroids for 1-3 days, subsequently obtaining SDCs. The cell morphology, proliferation rate, mitochondrial activity, and intracellular calcium levels were analyzed using flow cytometry, Seahorse metabolic assays, and spectrophotometry, while expression of cell progenitor and cardiac commitment genes were analyzed by quantitative PCR. Both healthy and pathological SDCs demonstrated significantly enhanced mitochondrial function-reflected by increased maximal respiration, ATP production, and coupling efficiency-along with reduced steady-state intracellular calcium levels compared with hmMSCs. SDCs from both healthy and dilated myocardium showed marked upregulation of several cardiac progenitor and lineage-commitment genes relative to hmMSCs. SDCs derived from both healthy and dilated myocardiums possess a more favorable metabolic, progenitor and cardiac commitment profile than conventional hmMSCs. hmMSCs and SDCs from dilated myocardium retain residual metabolic potential, which may be further enhanced under 3D culture conditions.