Advances in enhanced mesenchymal stem cell technologies: innovations and therapeutic applications

Mesenchymal stem cells (MSCs) have attracted considerable attention for clinical translation in regenerative medicine, primarily due to their validated paracrine effects, prominent immunomodulatory properties, and superior multipotent differentiation capabilities. However, the limited homing efficiency and poor post-transplant survival of MSCs severely compromise therapeutic efficacy, thereby giving rise to suboptimal and inconsistent treatment outcomes. To circumvent these critical drawbacks and fully harness the therapeutic potential of MSCs, researchers have incorporated a diverse array of effective strategies, including genetic engineering, preconditioning with cytokines, small molecular compounds or hypoxic stimuli, and scaffold-based culture systems. Given these promising research advances, this review systematically summarizes recent advances in MSC-enhanced therapeutic strategies, and elaborates on their core molecular mechanisms as well as how these mechanisms modulate MSC survival, homing capacity and immunomodulatory efficacy. On this basis, we further analyze the practical applicability of these enhanced MSCs in clinical trials and seek to provide critical insights for the clinical selection of MSC-based enhanced therapies.