Cells Versus Cell-Derived Signals in Cardiac Regenerative Therapy: A Comparative Analysis of Mechanisms and Clinical Evidence.

Heart failure (HF) and other cardiac pathologies represent leading causes of hospitalization and mortality worldwide, underscoring the urgent need for effective regenerative therapies. In recent years, considerable research has focused on developing cell-based therapeutic strategies, with stem cells receiving particular attention. Approaches that harness cellular signaling pathways have also been investigated. Experimental studies conducted in both animal models and human subjects have demonstrated that cell-based therapies hold remarkable potential, showing efficacy through improvements in cardiac function, patient quality of life, and overall safety. Clinical data concerning therapies based on cellular signals, while sometimes inconclusive, often yield outcomes comparable to or even superior to those of cell-based interventions. Nonetheless, both approaches face substantial challenges, including the need to ensure reproducibility of results, standardization of therapeutic product preparation, and addressing ethical and regulatory considerations. To translate these promising strategies into clinical practice, a greater number of large-scale, multicenter, and diverse clinical trials will be required.