From the bench to the bedside: mesenchymal stromal cells as immunoregulatory and regenerative therapies

Background Mesenchymal stromal cells (MSCs) have emerged as one of the most extensively studied adult stem cell populations, celebrated for their self-renewal, multilineage differentiation potential, and remarkable immunomodulatory properties. Originally discovered in bone marrow, MSCs are now known to reside in diverse tissues and have transitioned from experimental therapies to clinical applications for graft-versus-host disease (GVHD), autoimmune disorders, and regenerative medicine. However, despite the approval of several MSC products, enthusiasm is tempered by persistent challenges, including biological heterogeneity and inconsistent clinical efficacy. Main body This review comprehensively examines current knowledge on MSCs, evaluating their translational trajectory from preclinical discovery to clinical application. We first examine their biological foundations and molecular mechanisms, with a specific focus on paracrine signaling, extracellular vesicles-mediated effects, and the purinergic signaling axis. We then systematically assess their clinical applications across immune-mediated diseases, musculoskeletal disorders, and neurological conditions. Crucially, we analyze the “efficacy-expectation gap” between robust preclinical results and variable clinical outcomes, identifying key translational barriers such as donor variability, manufacturing standardization, and safety concerns regarding tumor progression. Conclusion MSCs represent a clinically promising yet biologically complex modality in modern medicine. While they offer undeniable therapeutic promise, realizing their full potential requires resolving fundamental uncertainties in biology and standardization. Future directions lie in the development of engineered MSCs, cell-free EVs therapeutics, and omics-driven precision applications. By integrating mechanistic insights with advanced biotechnology, MSCs can evolve from variable biologicals into reproducible, programmable agents for precision and regenerative medicine.