Fuente: PubMed "rice" J Am Heart Assoc. 2026 Apr 20:e045963. doi: 10.1161/JAHA.125.045963. Online ahead of print.ABSTRACTBACKGROUND: In ischemic heart failure, the biological mechanisms underlying the benefits of mesenchymal stromal cells (MSCs) and c-kit-positive cardiac progenitor cells (CPCs) remain incompletely understood.METHODS: In this predefined secondary biomarker analysis of 96 patients from the multicenter, randomized, double-blind, placebo-controlled Cardiovascular Cell Therapy Research Network CONCERT-HF (Combination of Mesenchymal and c-Kit+ Cardiac Stem Cells as Regenerative Therapy for Heart Failure) trial, plasma biomarkers were measured at baseline and at days 7, 30, and 180. Changes were assessed using 2-sample randomization median tests and multivariate 2-sample Cramér-von Mises tests to evaluate time point-specific and trajectory-level effects. Complementary longitudinal mixed-effects models were used to assess treatment×time interactions.RESULTS: Cell therapy induced distinct, time-dependent biomarker changes. Significant reductions were observed in TRAIL-R1 (tumor necrosis factor receptor superfamily member 10A; MSCs+CPCs), IL-33 (interleukin-33), and GDF-15 (growth differentiation factor 15; MSCs, CPCs), PTX3 (pentraxin 3; MSCs, and MSCs+CPCs), TNF-α (tumor necrosis factor-alpha; MSCs and MSCs+CPCs), and PDGF-BB (platelet-derived growth factor-BB; all cell therapy groups). VEGF-A (vascular endothelial growth factor A), HGF (hepatocyte growth factor), and BMP-9 (bone morphogenetic protein 9) also decreased significantly in the MSCs cohort. Multivariate 2-sample Cramér-von Mises test confirmed significant treatment-related shifts in biomarker trajectories for PTX3, TNF-α, PDGF-BB, GDF-15, BMP-9, and MMP-1 (matrix metalloproteinase-1). Complementary longitudinal mixed-effects modeling demonstrated significant treatment×time interactions for TNF-α, MMP-1, and BMP-9. Among individual contrasts, PDGF-BB showed the most consistent treatment effect, including a reduction in the MSCs group versus placebo at day 30 (estimate, -157.98 [95% CI, -286.04 to -29.91]; P=0.01). Time-specific treatment contrasts for most other biomarkers were modest with wide CIs. Greater increases in PDGF-BB at day 180 were associated with smaller improvements in Minnesota Living With Heart Failure Questionnaire scores.CONCLUSIONS: MSCs, CPCs, and their combination are associated with selective, time-dependent modulation of inflammatory and matrix remodeling biomarkers in ischemic heart failure. These findings provide mechanistic insight into cell therapy effects and identify PDGF-BB, PTX3, TNF-α, MMP-1, and BMP-9 as candidate biomarkers for response monitoring and hypothesis generation in future regenerative trials.REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02501811.PMID:42003602 | DOI:10.1161/JAHA.125.045963